# pos

id: cord-023402-8qfmo6rq
pos: .
token:
  .................................................................................................................................................................................................

lemma:
  .................................................................................................................................................................................................


id: cord-023402-8qfmo6rq
pos: .
token:
  ..................................................................................................................................................................................................

lemma:
  ..................................................................................................................................................................................................


# ent

id: cord-007375-hqmyund4
type: DNA
entity:
  Ϫ238 5 AAATCAGTCAGTGGCCCAGAA 3 5 TCATTCAACCAGC GGAAAACT 3 5 FAM CTCCCTGCTCCGATT MGB 3 and 5 VIC CTCCCTGCTCTGATT MGB 3


id: cord-007375-hqmyund4
type: DNA
entity:
  Ϫ308 5 GAAATGGAGGCAATAGGTTTTGAG 3 5 GTAGGACCCT GGAGGCTGAAC 3 5 FAM CCGTCCCCATGCC MGB 3 and 5 VIC CCGTCCTCATGCC MGB 3 for IL 10 Ϫ592 5 AGCTGAAGAGGTGGAAACATGTG 3 5 CAAGCAGCCC Differences


id: cord-023403-jzdrvfvr
type: ORG
entity:
  Flanders Interuniversity Institute for Biotechnology Department of Molecular and Cellular Interactions Free University of Brussels Brussels


id: cord-023403-jzdrvfvr
type: WORK_OF_ART
entity:
  The Effects of Hyperbaric Exposure on Human Peripheral Blood Mononuclear Cells with Special Emphasis on Natural Killer Cell Cytotoxicity and Subsets Materials


id: cord-000524-5y9kfyk9
type: DNA
entity:
  jir691 sha 2914c6a1f8f0bb25727bdfcd9a8a7b42d424d521 doc_id 524 cord_uid 5y9kfyk9 Background Mannose binding lectin MBL


id: cord-000524-5y9kfyk9
type: PROTEIN
entity:
  interferon IFN c macrophage inflammatory proteins MIP 1a MIP 1b monocyte chemotactic protein MCP 1 MCP 3


id: cord-000524-5y9kfyk9
type: ORG
entity:
  Dr K Takahashi Laboratory of Developmental Immunology Harvard Department of Pediatrics Massachusetts General Hospital Boston


id: cord-017438-x12d2ewc
type: DNA
entity:
  E coli Klebisella aerogenes Neisseria meningitides Staphylococcus aureus S pneumonia A fumigatus and C albicans c


id: cord-023438-g0k0vvdc
type: WORK_OF_ART
entity:
  The Effects of Hyperbaric Exposure on Human Peripheral Blood Mononuclear Cells with Special Emphasis on Natural Killer Cell Cytotoxicity and Subsets


id: cord-023439-r04y1j22
type: WORK_OF_ART
entity:
  The Role of Immune Complexes Consisting of Myelin Basic Protein MBP Anti MBP Antibodies and Complement in Promoting CD4 T cell Responses


id: cord-023417-by18aczt
type: GGP
entity:
  Scand J Immunol DOI 10 1111 j 0300 9475 2004 01423ae x sha c1a352fb40776f1d27a8fbc3a58b0d26b3236df3 doc_id 23417 cord_uid by18aczt


id: cord-023394-ptfjxpo6
type: ORG
entity:
  Mapping of the Ex Vivo Cellular Immune Response Against the Complete Human Parvovirus B19 Genome During Acute Infection


id: cord-023421-1d1gf7az
type: GGP
entity:
  Scand J Immunol DOI 10 1111 j 0300 9475 2004 01423bb x sha c672e03cd81dfbd3796fd8055b6e7bd016eff46b doc_id 23421 cord_uid 1d1gf7az Interferon α β IFN α β


id: cord-304626-ffao7vka
type: DNA
entity:
  human immunodeficiency virus Virus complement evasion strategies Complement and viral pathogenesis Viral


id: cord-278644-u4swxsjj
type: PROTEIN
entity:
  purified human complement component 4 Dodds 1993 in 100 μl BBS 2 4 mM barbital 145 mM NaCl 2 mM CaCl 2 1 mM MgCl 2 3 8


id: cord-268902-npug5c8p
type: PROTEIN
entity:
  hepatocyte asialoglycoprotein receptor Human mannose binding protein carbohydrate recognition domain


id: cord-268902-npug5c8p
type: GGP
entity:
  mannose 6 phosphate receptor Herpes simplex virus glycoprotein D acquires mannose 6 phosphate residues


id: cord-342176-tewfm8it
type: DNA
entity:
  High Capacity cDNA Archive kit Applied Biosystems Life Technologies Europe BV Naerum Denmark cat no 436881


id: cord-306111-wn1gxhk9
type: GGP
entity:
  Antigens DOI 10 1111 j 1399 0039 2006 00649 x sha 1468d0bcf3c567c4b3a7cb87cea974c8642f9669 doc_id 306111 cord_uid wn1gxhk9 The


id: cord-306111-wn1gxhk9
type: GGP
entity:
  lipooligosaccharide sialyation 16 17 Despite much progress in this area many puzzles remain to be addressed mostly related to the exact disposition of sugars on


id: cord-023445-c4tqioz1
type: GGP
entity:
  Scand J Immunol DOI 10 1111 j 0300 9475 2004 01423u x sha 2ae3ca6309f361ef1962ca9f3389af84332b3beb doc_id 23445 cord_uid c4tqioz1 Vitamins E and C


# bib

id: cord-000524-5y9kfyk9
author: Ling, Man To
date: 2011-11-11
txt: ./txt/cord-000524-5y9kfyk9.txt
cache: ./cache/cord-000524-5y9kfyk9.txt
extension: .txt
mime: text/plain
url: https://academic.oup.com/jid/article-pdf/205/1/44/18066273/jir691.pdf
doi: 10.1093/infdis/jir691
summary:
  Furthermore, MBL WT mice had enhanced production of proinflammatory cytokines and chemokines compared with MBL KO mice, suggesting that MBL could upregulate inflammatory responses that may potentially worsen pdmH1N1 and H9N2/G1 virus infections. In the present study, we investigated whether MBL could display any in vitro or in vivo antiviral function toward pdmH1N1 and H9N2/G1 viruses, as well as whether it could modulate the inflammatory response upon infection by these two strains of influenza virus. As shown in Figures 4 and 5 , upon pdmH1N1 and H9N2/G1 virus infection, inflammatory response assayed by cytokines and chemokines production was triggered in both MBL WT and MBL KO mice. Consistent with our cytokine and chemokine data, the pulmonary histological analysis suggested that the MBL WT mice had a more severe inflammatory response upon pdmH1N1 and H9N2/G1 virus infection.

title:
  Mannose-Binding Lectin Contributes to Deleterious Inflammatory Response in Pandemic H1N1 and Avian H9N2 Infection

abstract:
  Background. Mannose-binding lectin (MBL) is a pattern-recognition molecule, which functions as a first line of host defense. Pandemic H1N1 (pdmH1N1) influenza A virus caused massive infection in 2009 and currently circulates worldwide. Avian influenza A H9N2 (H9N2/G1) virus has infected humans and has the potential to be the next pandemic virus. Antiviral function and immunomodulatory role of MBL in pdmH1N1 and H9N2/G1 virus infection have not been investigated. Methods. In this study, MBL wild-type (WT) and MBL knockout (KO) murine models were used to examine the role of MBL in pdmH1N1 and H9N2/G1 virus infection. Results. Our study demonstrated that in vitro, MBL binds to pdmH1N1 and H9N2/G1 viruses, likely via the carbohydrate recognition domain of MBL. Wild-type mice developed more severe disease, as evidenced by a greater weight loss than MBL KO mice during influenza virus infection. Furthermore, MBL WT mice had enhanced production of proinflammatory cytokines and chemokines compared with MBL KO mice, suggesting that MBL could upregulate inflammatory responses that may potentially worsen pdmH1N1 and H9N2/G1 virus infections. Conclusions. Our study provided the first in vivo evidence that MBL may be a risk factor during pdmH1N1 and H9N2/G1 infection by upregulating proinflammatory response.


id: cord-007375-hqmyund4
title: Host Single-Nucleotide Polymorphisms and Altered Responses to Inactivated Influenza Vaccine
author: Tang, Yi-Wei
date: 2007-10-01
txt: ./txt/cord-007375-hqmyund4.txt
cache: ./cache/cord-007375-hqmyund4.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111848/
doi: 10.1086/521370
summary:
  We analyzed the relationship between host gene polymorphisms and responses in recipients of inactivated influenza vaccine, who were classified into poor, normal, or adverse response groups. The frequency of the mannose-binding lectin-2 codon 54 allele was significantly different among the 3 types of responders, with a decreased odds ratio for the development of poor or adverse responses (P = .033). The present study explored the possibility that host gene polymorphisms influence inactivated influenza vaccineinduced immune responses by comparing the frequencies of 8 SNPs in the MBL-2 gene and in the TNF-a and IL-10 promoter regions among different groups. We found a significant difference in allele frequency in the MBL-2 codon 54 among the poor, normal, and adverse responders, suggesting that the allele polymorphism is independently associated with poor and adverse responses to influenza vaccination. These findings support the present data by suggesting that the Ϫ1082 allele polymorphism in the IL-10 promoter region may be associated with adverse responses induced by influenza vaccine.

abstract:
  We analyzed the relationship between host gene polymorphisms and responses in recipients of inactivated influenza vaccine, who were classified into poor, normal, or adverse response groups. The frequency of the mannose-binding lectin-2 codon 54 allele was significantly different among the 3 types of responders, with a decreased odds ratio for the development of poor or adverse responses (P = .033). There was no statistical relationship between responses and either tumor necrosis factor-α or interleukin (IL)-10 promoter polymorphisms among the 3 response groups. When poor and normal responses were combined, the -1082 A allele in the IL-10 promoter conferred a significantly decreased risk of the development of adverse responses (P = .041). These data indicate that host polymorphisms play a role in determining responses to influenza vaccine.


id: cord-017438-x12d2ewc
title: MBL Deficiency as Risk of Infection and Autoimmunity
author: Gupta, Anita
date: 2012-03-20
txt: ./txt/cord-017438-x12d2ewc.txt
cache: ./cache/cord-017438-x12d2ewc.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122001/
doi: 10.1007/978-3-7091-1065-2_42
summary:
  The distribution of MBL gene polymorphisms was significantly different between patients with SARS and normal subjects, with a higher frequency of haplotypes associated with low or deficient serum levels of MBL in patients with SARS. Whether variant alleles of the MBL gene causing low serum concentrations of MBL are associated with increased susceptibility to RA and erosive outcome in an inception cohort of patients with early polyarthritis was studied by Jacobsen et al. SLE patients were associated with a reduced functional activity of the MBL pathway of complement, in relation to expression of MBL variant alleles, increased levels of autoantibodies against cardiolipin and C1q, but not against MBL. Polymorphisms of both codon 54 allele and promoter variants of the mannose MBL gene in patients with primary Sjogren''s syndrome (SS) was suggested as one of the genetic factors that determines susceptibility to SS (Wang et al. Association of mannose-binding lectin gene variation with disease severity and infections in a population-based cohort of systemic lupus erythematosus patients

abstract:
  In pathogen recognition by C-type lectins, several levels of complexity can be distinguished; these might modulate the immune response in different ways. Firstly, the pathogen-associated molecular pattern repertoire expressed at the microbial surface determines the interactions with specific receptors (Fig. 42.1). Secondly, each immune cell type possesses a specific set of pathogen-recognition receptors. Thirdly, changes in the cell-surface distribution of C-type lectins regulate carbohydrate binding by modulating receptor affinity for different ligands. Crosstalk between these receptors results in a network of multimolecular complexes, adding a further level of complexity in pathogen recognition (Cambi and Figdor 2005; Thiel et al. 2006) (see 10.1007/978-3-7091-1065-2_23). MBL deficiency is genetically determined and predisposes to recurrent infections and chronic inflammatory diseases. MBL deficiency has been implicated in susceptibility and course of viral, bacterial, fungal, and protozoan infection. More than 10% of the general population may, depending on definition, be classified as MBL deficient, underlining the redundancy of the immune system. MBL-disease association studies have been a fruitful area of research, which implicates a role for MBL in infective, inflammatory and autoimmune disease processes. MBL deficiency predisposes both to infection by extra-cellular pathogens and to autoimmune disease.


id: cord-022631-s4n24xij
title: Germinal Centres in Primary Sjögren''s Syndrome Indicate a Certain Clinical Immunological Phenotype
author: Jonsson, M. V.
date: 2008-06-28
txt: ./txt/cord-022631-s4n24xij.txt
cache: ./cache/cord-022631-s4n24xij.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159356/
doi: 10.1111/j.0300-9475.2004.01423h.x
summary:
  We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus.

abstract:
  Ectopic germinal centers (GCs) can be detected in the salivary glands of approximately 1/5 of patients with Sjögren's syndrome (SS) and appear in both primary and secondary SS. Previously, ectopic GC have been associated with increased local autoantibody production. The aim of this study was to determine whether GC in primary Sjögren's syndrome (pSS) defines a distinct seroimmunological phenotype. Retrospectively, a material of 130 haematoxylin and eosin‐stained paraffin‐embedded tissue sections of minor salivary gland tissue from patients with pSS was morphologically screened for the presence of ectopic GC. GC‐like lesions were detected in 33/130 (25%) of the pSS patients. Seventy‐two pSS patients lacking these structures (GC‐) were randomly selected for comparison. Focus score was significantly increased in the GC(+) patients compared to the GC(–) patients (P = 0.035). In the GC(+) group, 54.5% of the patients presented with anti‐Ro/SSA compared to 43.7% in the GC(–) group. Anti‐La/SSB was detected in 31.3% of the GC(+) patients compared to 25.7% of the GC(–) patients. Sixty‐one percentage of GC(+) patients presented with increased levels of IgG, a nonsignificant difference when compared to 39.4% in the GC(–) patients (P = 0.089). Levels of RF, ANA, ENA, IgM and IgA were similar in both patient groups, as were ESR and CRP. In conclusion, patients with ectopic GC have a higher focus score and more often present with autoantibodies and increased levels of IgG compared to pSS patients with regular focal infiltration (GC(–)). Our findings may indicate a certain seroimmunological phenotype and warrant for further prospective studies.


id: cord-023372-ft8cp9op
author: Rahman, Q. K.
date: 2008-06-28
txt: ./txt/cord-023372-ft8cp9op.txt
cache: ./cache/cord-023372-ft8cp9op.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169481/
doi: 10.1111/j.0300-9475.2004.01423aw.x
summary:
  We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus.

title:
  The Immunomodulatory Effect of Heat Shock Protein 70: Immunization with a DNA Construct Based on the Malarial Antigen Fused with a Fragment of HSP 70 Primes for a Th‐1 Type of Response

abstract:
  Finding an appropriate adjuvant for human vaccination is crucial. Heat shock proteins (HSPs) act as adjuvants when coadministered with peptide antigens or given as fusion proteins. However, there is a potential risk of autoimmunity when using the complete molecules, because HSPs are evolutionary conserved. To overcome this, we first evaluated the adjuvant effect against two different antigens of a less‐conserved fraction of Plasmodium falciparum HSP70 (Pf70C) and compared it to the whole HSP70 molecule from Trypanosoma cruzi (TcHSP70). We found that Pf70C exhibited similar adjuvant properties as the whole molecule. We later evaluated the adjuvant potential of Pf70C against the malarial antigen EB200 in a chimeric DNA construct. No appreciable levels of EB200‐specific antibodies were detected in mice immunized only with the DNA constructs. However, DNA primed the immune system, because subsequent challenge with the corresponding recombinant fusion proteins elicited a strong Th‐1 antibody response. In contrast, no priming effect was observed for ex vivo IFN‐γ production but stimulation with the HSP‐chimeric fusion protein induced a stronger secretion of IFN‐γin vitro than other proteins used. These results indicate that the use of HSPs is promising in the design of new vaccines.


id: cord-023373-6wh1kb3p
author: Melchjorsen, J.
date: 2008-06-28
txt: ./txt/cord-023373-6wh1kb3p.txt
cache: ./cache/cord-023373-6wh1kb3p.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169484/
doi: 10.1111/j.0300-9475.2004.01423r.x
summary:
  We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus.

title:
  Differential Requirements for Toll‐Like Receptor Signalling for Induction of Chemokine Expression by Herpes Simplex Virus and Sendai Virus

abstract:
  Toll‐like receptors (TLRs) are pattern recognition receptors of the innate immune system, which recognize molecular structures on pathogens or cellular stress‐associated molecules. TLR–ligand interactions trigger activation of inflammatory signal transduction and expression of genes involved in host defense. In this study, we have examined the requirement for different TLR adaptor molecules in virus‐induced chemokine expression and are currently trying to identify the TLR involved. We have found that both a herpesvirus [herpes simplex virus (HSV)] and a paramyxovirus (Sendai virus) require a functional genome to induce expression or proinflammatory chemokines in human and murine monocytic cell lines. For both viruses, this is independent of the TLR adaptor molecules TRIF and Mal. However, overexpression of the Vaccinia virus‐encoded inhibitor of TLR‐signalling A52R or dominant‐negative MyD88 totally inhibited HSV‐induced RANTES expression but only partially prevented Sendai virus from inducing this chemokine. This suggests that HSV‐induced RANTES expression occurs via a TLR pathways, whereas Sendai virus utilizes both TLR‐dependent and ‐independent pathways to stimulate expression of RANTES. We are currently trying to identify the TLRs involved. Data from these studies will also be presented at the meeting.


id: cord-023374-87ob1exq
author: Sukhija, S.
date: 2008-06-28
txt: ./txt/cord-023374-87ob1exq.txt
cache: ./cache/cord-023374-87ob1exq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169489/
doi: 10.1111/j.0300-9475.2004.01423ai.x
summary:
[cell repeats an earlier one in this file: 994 characters]

title:
  Levels, Complement Activity and Polymorphisms of Mannan‐Binding Lectin in Patients of Bronchial Asthma with Allergic Rhinitis

abstract:
  Activation of complement pathways, leading to production of C3a and C5a anaphylatoxins, has been postulated in the pathogenesis of asthma and allergic airway inflammation. The present study was undertaken to investigate the role of mannan‐binding lectin (MBL), an initiator of the lectin pathway of complement, in asthma and allergic rhinitis. MBL levels and MBL‐induced complement activity were determined in 19 patients of bronchial asthma with allergic rhinitis and 20 unrelated, age‐matched controls of Indian origin. MBL levels and activity were correlated with percent eosinophilia and percent predicted FEV1 values of the patients. Association of single nucleotide polymorphisms (SNPs) in exon 1 and intron 1 of the MBL with the disease, clinical markers, MBL levels and MBL‐induced complement activity was analysed using standard statistical tools. Significantly higher MBL levels and activity were observed in patients of bronchial asthma with allergic rhinitis as compared to the controls. We identified five SNPs, of which two, A816G in exon 1 and G1011A in intron 1 of the MBL, were novel. SNP G1011A was significantly associated with the disease (P = 0.0024, OR = 5.8696, 95% CI: 1.7316 < OR < 19.8963). Individuals with ‘A’ allele at position 1011 showed increased MBL levels, activity and disease severity. Our results suggest that ‘A’ allele at position 1011 leading to high MBL levels and complement activity may be contributing to the severity of bronchial asthma and allergic airway inflammation.


id: cord-023375-x4p187u7
author: Alitalo, A.
date: 2008-06-28
txt: ./txt/cord-023375-x4p187u7.txt
cache: ./cache/cord-023375-x4p187u7.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169490/
doi: 10.1111/j.0300-9475.2004.01423aj.x
summary:
[cell repeats an earlier one in this file: 994 characters]

title:
  Lysine‐Dependent Binding of OspE to the C‐terminus of Factor H Mediates Complement Resistance in Borrelia burgdorferi

abstract:
  Serum resistance of Borrelia burgdorferi strains belonging to the B. afzelii and B. burgdorferi sensu stricto genospecies is dependent on binding of complement inhibitor factor H. We recently reported that factor H binding by B. burgdorferi is due to inducible expression of several approximately 20 kDa plasmid‐encoded, surface‐exposed lipoproteins related to OspE (e.g. ErpA, ErpP and P21). In addition, a second class of factor H‐binding proteins of approximately 27–35 kDa has been described. The OspE‐related lipoproteins are dramatically induced by B. burgdorferi during transmission from its tick vector into the mammalian host. The induction of OspE‐related lipoproteins during mammalian infection may play a key a role in the borrelial evasion of the host's immune system. The goal of the present study was to define the factor H‐binding regions of OspE‐related proteins using mutagenesis, peptide mapping and surface plasmon resonance analysis (Biacore). The combined studies revealed that the C‐terminal regions of both human and mouse factor H (SCRs 18–20) specifically bind to OspE‐related lipoproteins. We also found FHR‐1, whose C‐terminal SCRs 3–5 are homologous to SCRs 18–20 of factor H, to bind to OspE. Peptide mapping revealed five putative regions (designated I‐V) in OspE that could directly interact with factor H. Deleting the C‐terminal 15 amino acid residues from region V of P21 abolished its ability to bind factor H. At the same time, however, synthetic peptides corresponding to the C‐termini of OspE, P21 and ErpP did not inhibit factor H binding to OspE. Thus, the C‐terminal‐binding region V appears to be necessary but not sufficient for factor H binding. When a more specific mutation strategy was employed, where single amino acid residues in peptides spanning over the factor H‐binding regions were mutated to alanines, we observed that lysines in the factor H‐binding regions of OspE were required for factor H binding. The combined data have revealed that key lysine residues in OspE‐related lipoproteins and ionic interactions are crucial for factor H interactions. Furthermore, binding of OspE to the C‐termini of both mouse and human factor H suggests that Borrelia spirochetes utilize analogous complement resistance mechanisms in both rodents and man. In Borrelia garinii strains, which in in vitro analyses have been found to be sensitive to complement killing, differences in the OspE sequences as well as in the expression of factor H‐binding proteins may account for their susceptibility to serum lysis.


id: cord-023387-tyeh14wz
title: Probiotic Bacteria Induce Regulatory Cytokine Production via Dendritic Cells
author: Hvas, C. L.
date: 2008-06-28
txt: ./txt/cord-023387-tyeh14wz.txt
cache: ./cache/cord-023387-tyeh14wz.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169507/
doi: 10.1111/j.0300-9475.2004.01423au.x
summary:
[cell repeats an earlier one in this file: 994 characters]

abstract:
  Probiotic bacteria, e.g. Lactobacillus spp., may improve diseases such as chronic inflammatory bowel disease. We examined cytokine production and phenotypic change after in vitro stimulation of T cells from healthy volunteers using different probiotic strains. Methods: T cells were cultured from colonic biopsies from eight healthy volunteers (Agnholt and Kaltoft, Exp Clin Immunogenet 2001;18:213–25), and dendritic cells were matured from their peripheral blood mononuclear cells. T‐cell cultures were stimulated with autologous bacterial sonicate or strains of Lactobacillus spp., with and without the addition of dendritic cells. Cytokine levels (TNF‐α, IFN‐γ, IL‐10 and GM‐CSF) and phenotype (CD3, CD4, CD25 and CD69) were measured on day 4. Results: Lactobacillus spp. induced higher productions of TNF‐α and IL‐10 than did autologous bacteria. In presence of dendritic cells, the production of all cytokines increased. However, the increases of IFN‐γ and TNF‐α were more pronounced in wells with autologous bacteria than in wells with Lactobacillus spp. The addition of dendritic cells upregulated CD25 expression without simultaneous upregulation of CD69. The upregulation was pronounced after stimulation with Lactobacillus rhamnosus GG compared with autologous bacteria and other lactobacilli. Discussion: In presence of dendritic cells, autologous bacteria induced inflammatory cytokines, while probiotics mainly induced regulatory cytokines. Lactobacillus rhamnosus GG induced a regulatory phenotype (cd25(+)), in part mediated by dendritic cells. Future studies will address whether this shift to a CD25(+) phenotype represents a differentiation into competent regulatory T cells. In a clinical context, such cells might be used for treatment of inflammatory diseases.


id: cord-023388-btbf6wkg
title: Decrease in Fine T‐cell Subset ratio MT2/MT1 During Steroid Reduction of Asthmatic Patients
author: Hoffmann, H. J.
date: 2008-06-28
txt: ./txt/cord-023388-btbf6wkg.txt
cache: ./cache/cord-023388-btbf6wkg.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169509/
doi: 10.1111/j.0300-9475.2004.01423ah.x
summary:
[cell repeats an earlier one in this file: 994 characters]

abstract:
  Combining inhaled long‐acting β‐2 agonist (LABA) and inhaled corticosteroid (ICS) seems to offer asthma control at a lower dose of ICS than achieved by ICS alone. Fine mapping of T‐cell surface markers by flow cytometry offers a detailed status of the individual's inflammatory response. The frequency of MT2 (CD4(+)CD45RA(–)CD62L(+)CD11adim) and MT1 (CD4(+)CD45RA(–)CD62L(–)CD11abright) cells in peripheral blood, and their ratio, has been shown to differ predictably in atopics and patients with leprosy, where MT2 correlates with a Th2 phenotype and MT1 with a Th1 phenotype. Stable asthmatics, requiring fluticasone propionate (FP) 750–1000 µg daily or equivalent, were randomized to receive, double‐blinded, either Seretide(®)[salmeterol and fluticasone propionate (SFC, n = 16)] 50 µg/500 µg bd or FP 500 µg bd (n = 17). If asthma was controlled based on lung function and symptoms at clinic visits every 6 weeks, ICS dose was tapered until asthma exacerbated or 0 µg was reached. The frequency and ratio of MT2 and MT1 T cells of the patients was monitored at 6 week intervals. As treatment tapered, the frequency of MT2 cells decreased (P = 0038 from first to final visit), whereas that of MT1 cells increased. The ratio of MT2/MT1 decreased (P = 0049 from first to final visit). In patients receiving LABA + ICS, the fall in MT2/MT1 ratio appeared to be more pronounced than in patients receiving ICS alone. Thus, the MT2 phenotype may be associated with stable asthma, whereas an imminent exacerbation may associate with an increase in the MT1 phenotype. LABA may allow for a greater effect of FP on the MT ratio.


id: cord-023389-ilrp8vb7
author: Wefer, J.
date: 2008-06-28
txt: ./txt/cord-023389-ilrp8vb7.txt
cache: ./cache/cord-023389-ilrp8vb7.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169512/
doi: 10.1111/j.0300-9475.2004.01423j.x
summary:
[cell repeats an earlier one in this file: 994 characters]

title:
  Protective DNA Vaccination Against MOG(91‐108)‐Induced Experimental Autoimmune Encephalomyelitis Involves Induction of IFNβ

abstract:
  DNA vaccine coding for the encephalitogenic peptide MOG(91‐108) protects LEW.1AV1 from subsequent development of experimental autoimmune encephalomyelitis (EAE). Protection is associated with a type 1 immune response and is dependent on the presence of CpG DNA motifs. The mechanisms underlying the observed reduction of EAE development in protected rats have not been fully clarified. We investigated immunological characteristics of lymphocytes after DNA vaccinaton and subsequent EAE induction. We confirm that protection was not associated with suppression of T1 cells, as transcription of the novel molecule rat T‐cell immunoglobulin‐ and mucin‐domain‐containing molecule (TIM‐3), reported to be exclusively expressed on differentiated T1 cells, was not altered by DNA vaccination. We did not note any clonal deletion upon tolerization, but detected an antigen‐specific lymphocyte population upregulating IFNγ upon recall stimulation 3 weeks after protective DNA vaccination. In protected rats, we observed (1) no alterations in antigen‐specific Th2 or Th3 responses, (2) reduced MHC II expression on splenocytes early after EAE induction, (3) antigen‐specific upregulation of IFNβ upon recall stimulation and (4) reduced IL‐12Rβ2 on lymphocytes. We thus demonstrate an association of the protective effect of DNA vaccination with expression of IFNβ. We are currently investigating the cellular mechanisms behind this IFNβ‐mediated protection.


id: cord-023390-5hcgdlmt
title: Inflammatory Cytokine Modulation of Cancer Cell Proliferation
author: Bhuvanath, S.
date: 2008-06-28
txt: ./txt/cord-023390-5hcgdlmt.txt
cache: ./cache/cord-023390-5hcgdlmt.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169513/
doi: 10.1111/j.0300-9475.2004.01423bi.x
summary:
[cell repeats an earlier one in this file: 994 characters]

abstract:
  Inflammatory cytokines have a critical role in modulation of both innate and adaptive immunity in response to foreign antigen. They also play an important role in anticancer immunity. For example, they can promote cell‐mediated immunity against cancer cells. With their immunostimulatory effects, these cytokines are being tested for cancer treatment in the form of DNA vaccine or adjuvant or therapeutic cytokines. Direct effect of these cytokines on cancer cell, however, is still unclear. In this project, we investigated whether IL‐1( and IL‐18 can modulate cancer cell proliferation. We employed a simple nonradioactive proliferation (MTT) assay and detection of lactate dehydrogenase (LDH) to test the effect of these recombinant human cytokines on various cancer cell lines, including breast cancer cell line (MCF‐7), oral carcinoma cell line (KB), colon cancer cell line (Caco‐2) and choriocarcinoma cell line (Jar). Cytokines used in this study had both inhibitory and stimulatory effect on cell proliferation. Findings in this project could provide an insight of cancer cell response to these cytokines and this could lead to a consideration on using cytokine as immunotherapy for cancer treatment.


id: cord-023391-bq5w3jk9
author: Utermöhlen, O.
date: 2008-06-28
txt: ./txt/cord-023391-bq5w3jk9.txt
cache: ./cache/cord-023391-bq5w3jk9.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169516/
doi: 10.1111/j.0300-9475.2004.01423l.x
summary:
[cell repeats an earlier one in this file: 994 characters]

title:
  Delayed Elimination of the LCM Virus from Acid Sphingomyelinase‐Deficient Mice due to Reduced Expansion of Virus‐Specific CD8(+) T Lymphocytes

abstract:
  The phagolysosomally localized acid sphingomyelinase (ASMase) activated by proinflammatory cytokines such as TNF and IFN‐γ generates the signalling molecule ceramide which in turn results in the activation of proteases like cathepsin D. These characteristics of ASMase suggest a possible role of this molecule in the phagocytotic uptake and phagosomal degradation processes of antigens or in antigen presentation. We show here that ASMase(–/–) mice fail to eliminate the noncytopathic lymphocytic choriomeningitis (LCM) virus as rapidly as littermate wildtype mice. Investigation of the immune response revealed a reduced expansion of CD8(+) T cells. The secretion of IFN‐γ in response to contact with target cells as well as the cytolytic activity of virus‐specific CD8(+) T cells was severely impaired. Additionally, both phases of the LCM virus‐specific DTH response, mediated by CD8(+) and CD4(+) T cells consecutively, were diminished in ASMase(–/–) mice. However, the secondary memory response of virus‐specific CTL was not altered, and the virus was effectively controlled for at least 3 months by ASMase(–/–) mice. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus‐specific CD8(+) T cells during the acute infection of mice with the LCM virus.


id: cord-023392-axd0901z
title: Association between Mannose‐Binding Lectin and Vascular Complications in Type 1 Diabetes
author: Hansen, T. K.
date: 2008-06-28
txt: ./txt/cord-023392-axd0901z.txt
cache: ./cache/cord-023392-axd0901z.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169517/
doi: 10.1111/j.0300-9475.2004.01423i.x
summary:
[cell repeats an earlier one in this file: 994 characters]

abstract:
  Complement activation and inflammation have been suggested in the pathogenesis of diabetic vascular lesions. We investigated serum mannose‐binding lectin (MBL) levels and polymorphisms in the MBL gene in type 1 diabetic (T1DM) patients with and without diabetic nephropathy and associated macrovascular complications. Polymorphisms in the MBL gene and serum MBL levels were determined in 199 T1DM patients with overt nephropathy and 192 T1DM patients with persistent normoalbuminuria matched for age, sex and duration of diabetes as well as in 100 healthy control subjects. The frequencies of high and low expression MBL genotypes were similar in patients with T1DM and healthy controls. High MBL genotypes were significantly more frequent in diabetic patients with nephropathy than in the normoalbuminuric group, and the risk of having nephropathy, given a high MBL genotype, assessed by odds ratio was 1.52 (1.02–2.27), P = 0.04. Median serum MBL concentrations were significantly higher in patients with nephropathy than in patients with normoalbuminuria [2306 µg/l (IQR 753–4867 µg/l) versus 1491 µg/l (IQR 577–2944), P = 0.0003], and even when comparing patients with identical genotypes, serum MBL levels were higher in the nephropathy group than in the normoalbuminuric group. Patients with a history of cardiovascular disease had significantly elevated MBL levels independently of nephropathy status [3178 µg/l (IQR 636–5231 µg/l) versus 1741 µg/l (IQR 656–3149 µg/l), P = 0.02]. The differences in MBL levels between patients with and without vascular complications were driven primarily by pronounced differences among carriers of high MBL genotypes (P < 0.0001). Our findings suggest that MBL may be involved in the pathogenesis of microvascular and macrovascular complications in type 1 diabetes and that determination of MBL status might be used to identify patients at increased risk of developing these complications.


id: cord-023393-8nye3nc8
title: Mannan‐Binding Lectin, L‐Ficolin and H‐Ficolin Selectively Binds to Different Bacteria
author: Krarup, A.
date: 2008-06-28
txt: ./txt/cord-023393-8nye3nc8.txt
cache: ./cache/cord-023393-8nye3nc8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169518/
doi: 10.1111/j.0300-9475.2004.01423al.x
summary:
[cell repeats an earlier one in this file: 994 characters]

abstract:
  Mannan‐binding lectin (MBL), L‐ficolin and H‐ficolin are pattern recognition molecules of the innate immune system. We investigated the ability of these molecules to bind to different serotypes and noncapsulated variants of Streptococcus pneumonia and Staphylococcus aureus. We found that MBL binds to noncapsulated S. aureus strain (Wood) but not any of the examined S. pneumoniae serotypes. L‐ficolin binds to some capsulated S. pneumoniae serotypes (11A, 11D and 11F) as well as some capsulated S. aureus serotypes (Type‐1, ‐8, ‐9, ‐11 and ‐12). H‐ficolin does not bind to any of the examined S. pneumoniae and S. aureus serotypes included in this study but did bind to a strain of Aerococcus viridans. When bound to bacteria, MBL and H‐ficolin initiated activation of complement factor C4, whereas L‐ficolin did not. During this study, quantitative assays for the three proteins were developed and the concentration in 97 plasma samples were determined and the median values were estimated at 0.8 μg of MBL/ml, 3.3 μg of L‐ficolin/ml and 18.4 μg of H‐ficolin/ml, respectively.


id: cord-023394-ptfjxpo6
author: Isa, A.
date: 2008-06-28
txt: ./txt/cord-023394-ptfjxpo6.txt
cache: ./cache/cord-023394-ptfjxpo6.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169519/
doi: 10.1111/j.0300-9475.2004.01423n.x
summary:
[cell repeats an earlier one in this file: 994 characters]

title:
  Mapping of the Ex Vivo Cellular Immune Response Against the Complete Human Parvovirus B19 Genome During Acute Infection

abstract:
  Background: Human parvovirus B19 (B19) is a ubiquitous pathogen, normally causing a mild self‐limiting disease, but also capable of causing both significant pathology and long‐term persistence. The small size and stability of the virus makes it suitable for mapping of the full breath and the kinetics of the cellular immune responses following acute viral infection. Methods: Five patients with acute primary B19 infection were included in the study and followed consecutively for up to 200 weeks. Cellular immune responses were mapped by IFNγ enzyme‐linked immunospot to overlapping peptides spanning the whole B19 genome. Results: In all five acutely infected patients, we were able to monitor the kinetics of a strong specific cellular immune reaction. Responses peaked at levels of 850–1850 SFC/million PBMCs, roughly corresponding to 0.3–0.6% B19‐specific CD8(+) cells circulating in peripheral blood at 10–80 weeks post‐infection. The responses in individual patients were directed to three or four different peptide pools, and the specificity was confined to the same CD8 epitopes present in the pools throughout the follow‐up period. The majority of responses were directed to the virus nonstructural protein, only two patients showed any response to the capsid proteins, elicited by the same epitope in both cases. Conclusion: The cellular immune responses to acute B19 infection are surprisingly narrow in distribution and remain at high levels for up to 80 weeks post‐infection. The initial epitope specificity is maintained, and the majority of responses target the virus nonstructural protein, which is not included in vaccine preparations, evaluated against the infection.


id: cord-023402-8qfmo6rq
author: Reinholdt, J.
date: 2008-06-28
txt: ./txt/cord-023402-8qfmo6rq.txt
cache: ./cache/cord-023402-8qfmo6rq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169534/
doi: 10.1111/j.0300-9475.2004.01423t.x
summary:
[cell repeats an earlier one in this file: 994 characters]

title:
  Pneumococcal IgA1 Protease Activity Interferes with Opsonophagocytosis of Streptococcus Pneumoniae Mediated by Serotype‐Specific Human Monoclonal IgA1 Antibodies

abstract:
  Bacteria‐specific IgA antibodies are efficient opsonins for neutrophils and mononuclear phagocytes, provided that the phagocytes express the Fca receptor (CD89). Expression of CD89 can be stimulated by inflammatory cytokines, activated complement factors and certain microbial components. In one study, unstimulated phagocytes were able to ingest IgA antibody‐treated pneumococci, but only in the presence of complement, which was found to be activated by the IgA antibodies along the alternative pathway. Pneumococci produce IgA1 protease that cleaves human IgA1, but not IgA2, molecules in the hinge region. This leaves IgA1 as Fabα (monovalent) deprived of Fcα which contains the docking site for CD89. IgA1 is the vastly predominant subclass of IgA in the upper airways and circulation of humans. Aims: To examine the effects of IgA1 protease activity and complement on phagocytosis of IgA antibody‐coated pneumococci by an unstimulated human phagocytic cell line (hl60). Materials and methods: IgA1 and IgA2 monoclonal antibodies to serotype 4 pneumococcal capsular polysaccharide (ps) were generated by heterohybridoma technique involving B cells from human vaccinees. Isogenic serotype 4 pneumococci with and without IgA1 protease activity, respectively, were obtained after inactivation of the iga gene of the TIGR4 strain. Opsonophagocytosis was quantitated using the assay described by Romero‐Steiner et al. Based on enumeration of surviving bacteria by culture. The integrity of IgA molecules was examined by western blotting. Results: Both IgA1 and IgA2 antibody to type‐4 polysaccharide‐induced phagocytosis of IgA1 protease‐deficient type‐4 pneumococci equally well in the absence as in the presence of complement. Iga1 antibody to type‐4 polysaccharide displayed a fourfold higher opsonophagocytosis titer against IgA1 protease deficient compared to homologous wildtype target bacteria. A similar effect of IgA1 protease activity of the target bacteria was not observed in a parallel experiment where IgA2 antibody to type‐4 polysaccharide served as opsonin. IgA1 antibody extracted from IgA1 protease‐producing target bacteria was almost exclusively in the form of Fabα. Conversely, IgA1 from protease‐deficient bacteria and IgA2 from both types of bacteria were intact. Conclusions: These results indicate that the IgA1 protease activity of S. neumoniae may help the bacteria escape IgA1 antibody‐mediated opsonophagocytosis. Besides, in these experiments, IgA‐mediated opsonophagocytosis was independent of complement.


id: cord-023403-jzdrvfvr
author: Ahlfors, E.
date: 2008-06-28
txt: ./txt/cord-023403-jzdrvfvr.txt
cache: ./cache/cord-023403-jzdrvfvr.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169538/
doi: 10.1111/j.0300-9475.2004.01423ac.x
summary:
[cell repeats an earlier one in this file: 994 characters]

title:
  Proliferation of Cells in the Oral Mucosa, the Ear Skin and the Regional Lymph Nodes in Mice Sensitized and Elicited with a Hapten

abstract:
  During contact sensitivity reaction, immune cells proliferate. In order to study the histological picture of these proliferation phases, we used a mouse model of contact sensitivity in the oral mucosa and on skin. We also used bromodeoxyuridin (BrdU, an analogue to thymidin) that is incorporated into the nucleus during cell replication. The hapten oxazolone (OXA) was used to sensitize and elicit the oral mucosa and/or the ear skin. Mice were killed at various times after elicitation, and unsensitized animals were also exposed to the hapten as controls. BrdU (25 mg/kg animal) was injected i.p. 2 h before the kill. Specimens from the oral mucosa, ear skin and submandibular and auricular lymph nodes were cut and fixed in 4% paraformaldehyde. They were then treated with acid and biotinylated anti‐BrdU antibody and developed using ABC‐kit and DAB. The analyses were performed using a Leica light microscope and the computer program analysis. In the oral mucosa, the frequency of proliferating cells were increasing during the observation period, 4–24 h after elicitation, regardless of site of sensitization. The proliferating cells were found mainly in the basal cell layer of the epithelium. Similar patterns were found in ear skin. The regional lymph nodes demonstrated a few scattered proliferating cells 4 h after elicitation. After 24 h, these cells were found frequently in the whole lymph node. Control animals exhibited considerable less proliferating cells at all times. We conclude that most proliferating cells were found 24 h after elicitation locally at the hapten‐exposed sites (the oral mucosa or the ear skin) as well as in the regional lymph nodes.


id: cord-023407-s85g7g0x
author: Huang, Y.‐M.
date: 2008-06-28
txt: ./txt/cord-023407-s85g7g0x.txt
cache: ./cache/cord-023407-s85g7g0x.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169544/
doi: 10.1111/j.0300-9475.2004.01423d.x
summary:
[cell repeats an earlier one in this file: 994 characters]

title:
  Anti‐Inflammatory Liver X Receptors and Related Molecules in Multiple Sclerosis Patients from Sardinia and Sweden

abstract:
  The nuclear receptor heterodimers of liver X receptors (LXRs) are recently identified as key transcriptional regulators of genes involved in lipid homeostasis and inflammation. LXRs and their ligands are negative regulators of macrophage inflammatory gene expression. Multiple sclerosis (MS), a demyelinating disease of the central nervous system of unknown cause, is characterized by recurrent inflammation involving macrophages and their inflammatory mediators. Sweden belongs to the countries with a high MS incidence. In Italy, incidence is lower, with an exception for Sardinia where the incidence is even higher than that in Sweden. Subjects from Sardinia are ethnically more homogeneous and differ from Swedes, also regarding genetic background and environment. We studied LXRs and their related molecules of blood mononuclear cells (MNCs) from female patients with untreated relapsing‐remitting MS from Sassari, Sardinia and Stockholm, Sweden. Sex‐ and age‐matched healthy controls (HCs) were from both areas. mRNA expression was evaluated by real‐time PCR. LXR‐α was lower (P < 0.05) in MS (mean ± SEM: 3.1 ± 0.2; n = 37) compared to HC (3.6 ± 0.1; n = 37). LXR‐α was lower in MS from Stockholm (2.6 ± 0.2; n = 22) compared to corresponding HC (3.4 ± 0.1; n = 22; P < 0.01) and compared to MS (3.8 ± 0.2; n = 15; P < 0.001) and HC (4 ± 0.2; n = 15; P < 0.001) from Sardinia. MS patients from Stockholm, but not from Sassari, also expressed lower (P < 0.05) LXR‐β (−4.1 ± 0.4) compared to corresponding HC (−2.9 ± 0.3). MS from Stockholm was associated with higher ABCA‐1 (6.1 ± 0.4 versus 5.0 ± 0.3; P < 0.05) and higher estrogen receptor‐β‐Cx (2.4 ± 0.4 versus 0.8 ± 0.4; P < 0.01) compared to corresponding HC. The HC from Sassari had higher androgen receptor (2.9 ± 0.2) compared to MS from Sassari (1.4 ± 0.3; P < 0.01), MS (1.3 ± 0.4; P < 0.01) and HC from Stockholm (1.2 ± 0.3; P < 0.01). MS from Sassari had lower cyclooxygenase‐1 compared to corresponding HC (5.1 ± 0.4 versus 6.6 ± 0.3; P < 0.01) and lower prostaglandin‐E (−0.03 ± 0.5) compared to the HC (1.4 ± 0.5; P < 0.05) and MS (2.7 ± 0.4; P < 0.05) and HC from Stockholm (1.9 ± 0.4, P < 0.001). Our findings identify LXRs and their related molecules as being involved in MS from Stockholm but not from Sassari, while sex hormone receptors seem to be involved in MS in Sassari.


id: cord-023410-eblcf902
title: Clonally Expanded CD8(+) T cells in Allogeneic Bone Marrow Transplantation
author: Kollgaard, T. M.
date: 2008-06-28
txt: ./txt/cord-023410-eblcf902.txt
cache: ./cache/cord-023410-eblcf902.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169548/
doi: 10.1111/j.0300-9475.2004.01423bm.x
summary:
[cell repeats an earlier one in this file: 994 characters]

abstract:
  Allogeneic bone marrow transplantation (BMT) is a potentially curative therapy for patients with haematologic malignancies. Several lines of evidence demonstrate that donor T cells are involved in the antitumour effects observed after BMT. Thus, patients receiving T‐cell‐depleted BMT have a higher risk of leukaemia relapse compared to patients receiving nonmanipulated BMT, and patients experiencing graft‐versus‐host disease (GVHD) have a lower risk of disease relapse than patients who do not experience GVHD. Although the importance of donor T cells for the curative action of BMT has been established, the exact mechanisms and molecules involved in this graft‐versus‐tumour effect remain largely unknown. In a recently initiated project, we have conducted a longitudinal study of T‐cell clonotypes in patients who received peripheral blood stem cell grafts after nonmyeloablative conditioning. Peripheral blood samples were obtained sequentially after transplant, and the mononuclear cells (MNCs) were isolated and cryopreserved. CD8(+) T cells were isolated from the MNCs by use of immunomagnetic beads or FACS and analysed for the presence of clonally expanded cells by T‐cell receptor clonotype mapping based on RT‐PCR and denaturing gradient gel electrophoresis (DGGE). Using this gel‐based methodology, clonally expanded T cells were monitored after transplant and compared to the clinical data of the patients. The preliminary results demonstrates the presence of clonally expanded CD8(+) T cells at all time points analysed. Furthermore, a number of clonotypes persisted for more than 6 months, and other clonotypes emerged during this period. The appearance of newly emerged clonotypes which coincided with clinical GVHD could indicate a role for these T cells in the pathogenesis of GVHD.


id: cord-023411-iszb5qlk
title: Presence of Helicobacter pylori Antibodies in Haemodialysis Patients
author: Astrinidou‐Vakaloudi, A.
date: 2008-06-28
txt: ./txt/cord-023411-iszb5qlk.txt
cache: ./cache/cord-023411-iszb5qlk.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169550/
doi: 10.1111/j.0300-9475.2004.01423p.x
summary:
[cell repeats an earlier one in this file: 994 characters]

abstract:
  Aim: Renal dysfunction may influence the colonization of gastric mucosa by urea‐splitting bacteria such as Helicobacter pylori, by increasing urea concentrations in the gastric juice. Our aim was to investigate the prevalence of H. pylori in patients with end‐stage renal disease (ESRD), receiving long‐term haemodialysis treatment. Methods: This study included 40 sera from patients with ESRD (29 male and 11 female) undergoing periodic haemodialysis; mean time of treatment was 42.6 months. Using ELISA technique, we investigated the presence of IgG and IgA antibodies against H. pylori as well as IgG CagA (antibodies specific for CagA(+) strains of H. pylori). Sera from 40 healthy blood donors were used as a control group. Results: H. pylori IgG antibodies were detected in 32 out of 40 (80%) patients in the dialysis group, while 31/40 (77.5%) tested positive for IgA. IgG CagA antibodies were present in 13 out of 40 (32.5%). Prevalence of H. pylori IgG, IgA and CagA IgG antibodies in the control group was 33, 7 and 15%, respectively. Conclusions: Although international data suggest that prevalence of H. pylori infection is the same in ESRD patients as in healthy individuals, in our study that seems not to be the case. The higher blood and gastric juice urea levels may be a risk factor (among many others), but more studies are required in order to understand the relation of H. pylori infection in this group of patients.


id: cord-023414-xxw5kptr
author: Chistensen, H. R.
date: 2008-06-28
txt: ./txt/cord-023414-xxw5kptr.txt
cache: ./cache/cord-023414-xxw5kptr.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169554/
doi: 10.1111/j.0300-9475.2004.01423ap.x
summary:
[cell repeats an earlier one in this file: 994 characters]

title:
  Characterization of a Large Panel of Lactic Acid Bacteria Derived from the Human Gut for their Capacity to Polarize Dendritic Cell

abstract:
  Dendritic cells (DCs) are the principal stimulators of naïve T helper (Th) cells and play a pivotal regulatory role in the Th1, Th2 and Treg cell balance. DCs are present in the gut mucosa and may thus be target for modulation by gut microbes, including ingested probiotics. Here, we tested the hypothesis that species of lactic acid bacteria, important members of the gut flora, differentially activate DC. A large panel of human gut‐derived Lactobacillus and Bifidobacterium spp. was screened for DC‐polarizing capacity by exposing bone marrow‐derived murine DC to lethally irradiated bacteria. Cytokines in culture supernatants and DC‐surface maturation markers were analysed. Substantial differences were found among strains in the capacity to induce interleukin‐12 (IL‐12) and tumour necrosis factor (TNF)‐α, while the differences for IL‐10 and IL‐6 were less pronounced. Bifidobacteria tended to be weak IL‐12 and TNF‐α inducers, while both strong and weak IL‐12 inducers were found among the strains of Lactobacillus. Remarkably, strains weak in IL‐12 induction inhibited IL‐12 and TNF‐α production induced by an otherwise strong cytokine‐inducing strain of Lactobacillus casei, while IL‐10 production remained unaltered. Selected strains were tested for induction of DC maturation markers. Those lactobacilli with greatest capacity to induce IL‐12 were most effective in upregulating surface MHC class II and CD86. Moreover, L. casei‐induced upregulation of CD86 was reduced in the presence of a weak IL‐12‐inducing L. reuteri. In conclusion, human Lactobacillus and Bifidobacterium spp. polarize differentially DC maturation. Thus, the potential exists for Th1/Th2/Treg‐driving capacities of the gut DC to be modulated according to composition of gut flora including ingested probiotics.


id: cord-023415-hhvmsn5b
author: Karlsson, H.
date: 2008-06-28
txt: ./txt/cord-023415-hhvmsn5b.txt
cache: ./cache/cord-023415-hhvmsn5b.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169557/
doi: 10.1111/j.0300-9475.2004.01423at.x
summary:
[cell repeats an earlier one in this file: 994 characters]

title:
  Pattern of Cytokine Responses to Gram‐Positive and Gram‐Negative Commensal Bacteria is Profoundly Changed when Monocytes Differentiate into Dendritic Cells

abstract:
  The normal gastrointestinal flora is crucial for the maturation of the acquired immunity via effects on antigen‐presenting cells (APCs). Here, we have investigated how two types of APCs, monocytes and dendritic cells (DCs), react to different bacterial strains typical of the commensal intestinal flora. Purified monocytes and monocyte‐derived DCs were stimulated with UV‐inactivated gram‐positive (Lactobacillus plantarum and Bifidobacterium adolescentis) and gram‐negative (Escherichia coli and Veillonella parvula) bacterial strains. Monocytes produced higher levels of IL‐12p70 and TNF, as detected by ELISA, in response to L. plantarum than to E. coli and V. parvula. In contrast, DCs secreted high amounts of IL‐12p70, TNF, IL‐6 and IL‐10 in response to E. coli and V. parvula but were practically unresponsive to L. plantarum and B. adolescentis. The lack of response to the gram‐positive strains correlated with a lower surface expression of Toll‐like reseptor 2 (TLR2) on DCs compared to monocytes. The surface expression of TLR4 on DCs was undetectable when analysed by flow cytometry, but blocking this receptor decreased the TNF production in response to V. parvula, indicating that low TLR4 expression on DCs is sufficient to mount an inflammatory response to gram‐negative bacteria. IFN‐γ increased the expression of TLR4 on DCs and also potentiated the cytokine response to gram‐negative bacteria. Our results indicate that, when monocytes differentiate into DCs, their ability to respond to different commensal bacteria dramatically changes, thereby becoming unresponsive to probiotic gram‐positive bacteria. These results may have important implications for the capacity of different groups of commensal bacteria to regulate mucosal and systemic immunity.


id: cord-023417-by18aczt
author: Vilhelmsson, M.
date: 2008-06-28
txt: ./txt/cord-023417-by18aczt.txt
cache: ./cache/cord-023417-by18aczt.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169559/
doi: 10.1111/j.0300-9475.2004.01423ae.x
summary:
[cell repeats an earlier one in this file: 994 characters]

title:
  The Malassezia sympodialis Allergen Mala s 11 with Sequence Similarity to Manganese Superoxide Dismutase Induces Maturation and Production of Inflammatory Cytokines in Human Dendritic Cells

abstract:
  The chronic inflammatory skin disease atopic eczema (AE) affects almost 15% of the population in many countries today. The pathogenesis of AE is not fully understood. A combination of genetic predisposition and environmental factors like microorganisms seems to contribute to the symptoms. The yeast Malassezia sympodialis is part of our normal skin micro flora but can act as an allergen and elicit specific IgE and T‐cell reactivity in patients with AE. Recently, we identified a novel major M. sympodialis allergen, designated Mala s 11 (22.4 kDa), with sequence similarity to the mitochondrial enzyme manganese superoxide dismutase (MnSOD). Interestingly, Mala s 11 has a high degree of homology to human MnSOD. The aim of this study was to examine the effects of recombinant Mala s 11 on antigen‐presenting dendritic cells. Monocyte‐derived dendritic cells (MDDCs) from healthy blood donors were cultured with or without Mala s 11 for different time periods. It was found that the maturation marker CD83 and the costimulatory molecules CD80 and CD86 were upregulated on the MDDCs exposed to Mala s 11 for 24 h, as demonstrated by flow cytometry. Furthermore, coculture of MDDCs with Mala s 11 for 9 h induced an increased production of the inflammatory cytokines IL‐6 (200‐fold), TNF‐α (100‐fold) and IL‐8 (sixfold), as detected by the cytometric bead array (CBA) analysis. Our results suggest that Mala s 11 affects the immune response through DC maturation and production of inflammatory cytokines. The potential cross‐reactivity with human MnSOD needs to be explored and the exact role of Mala s 11 in the pathogenesis of AE assessed in clinical studies involving skin prick and atopy patch tests.


id: cord-023419-lnmc6vv5
author: Steinhauer, C.
date: 2008-06-28
txt: ./txt/cord-023419-lnmc6vv5.txt
cache: ./cache/cord-023419-lnmc6vv5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169563/
doi: 10.1111/j.0300-9475.2004.01423ax.x
summary:
[cell repeats an earlier one in this file: 994 characters]

title:
  High‐Throughput Proteomics on Antibody‐based Microarrays: the Importance of Probe and Surface Design

abstract:
  In analogy to DNA microarrays, protein microarrays offer a new distinct possibility to perform sensitive high‐throughput global proteome analysis. However, the development of the protein microarray technology will place high demands upon the design of both probes and solid supports. The analysis of thousands of heterogeneous proteins on a single microarray requires the use of uniform probes, such as antibodies, directly designed for protein microarray applications. We have recently generated a human recombinant single‐chain Fv antibody library, genetically constructed around one framework, the nCoDeR‐library, containing 2 × 1010 clones. Single framework antibody fragments (sinFabs) selected from this library were successfully applied as probes for microarrays providing sensitive detection in the 600 attomol (mass spectrometry) and the 300 zeptomole range (fluorescence). However, the choice of framework is critical. We have shown that the selected nCoDeR framework displayed excellent functional on‐chip stability and arrayed dehydrated probes retained their activity for several months. Furthermore, we have addressed the issues of biocompatibility of the solid support and immobilization strategies for our microarray setup. An in‐house‐designed substrate, macroporous silicon coated with nitrocellulose (MAP3‐NC7), displayed properties equal to, or better than, those of five commercially available supports used as reference surfaces. We have also evaluated different coupling strategies, such as adsorption, covalent coupling, diffusion and affinity coupling. Using a novel affinity tag, the double‐(his)6‐tag, we increased the binding efficiency of sinFab‐molecules to Ni2(+)‐coated solid supports, thereby allowing nonpurified probes to be directly applied.


id: cord-023421-1d1gf7az
title: Monitoring Patients Treated with Type 1 Interferons: Antiviral versus MxA Induction Assays
author: Sønder, S. U. S.
date: 2008-06-28
txt: ./txt/cord-023421-1d1gf7az.txt
cache: ./cache/cord-023421-1d1gf7az.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169566/
doi: 10.1111/j.0300-9475.2004.01423bb.x
summary:
[cell repeats an earlier one in this file: 994 characters]

abstract:
  Interferon‐α/β (IFN‐α/β) is increasingly used as antiviral and immunomodulatory therapies. Unfortunately, bioavailability varies with IFN species and mode of administration, and all IFN species are potentially immunogenic. Assays for antiviral activity (IFN) and antiviral neutralization (antibodies, NAb) have been used for some time to monitor patients on IFN biologicals. These assays require laborious titrations making them unsuitable for large‐scale clinical use. Our laboratories have therefore modified the antiviral assays for IFN bioactivity and Nab, so that they are suitable for large‐scale screening in specialized laboratories. The read‐out is survival of a subcloned A549 cell line in the presence of an otherwise lethal amount of virus. Thus, survival increases in the presence of type 1 IFN and decreases in the presence of NAb against the IFN added to the cells. MxA is induced by type 1 IFN and can be used for measuring the Nab activity. In another assay, the MxA level in the A549 cell line is measured. In an attempt to find a new and better reporter gene for type 1 IFN than MxA and genes specific for either IFN‐α or ‐β, a micro array screen was carried using the U133A chip from Affymetrix. The expression of 22,000 genes can be studied simultaneous with this technology. The results will be presented at the conference.


id: cord-023425-3sjsogvq
title: Do High and Low Tumour Necrosis Factor‐α Responders Exist in Dairy Cows?
author: Røntved, C. M.
date: 2008-06-28
txt: ./txt/cord-023425-3sjsogvq.txt
cache: ./cache/cord-023425-3sjsogvq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169577/
doi: 10.1111/j.0300-9475.2004.01423v.x
summary:
[cell repeats an earlier one in this file: 994 characters]

abstract:
  A whole blood stimulation assay with Escherichia coli (O111:B4) endotoxin was established to measure the capacity of dairy cows to produce the proinflammatory cytokine tumour necrosis factor‐α (TNF‐α) ex vivo. Initially, a time‐ and dose‐dependent study was carried out to find the optimal stimulation conditions for the TNF‐α response. The TNF‐α response peaked between 3 and 4 h at 38.5 °C. A dose in the range of 5–10 g of E. coli lipopolysaccharide (LPS)/ml whole blood was found to give the maximum TNF‐α response. Thirty‐eight Danish–Holstein dairy cows were investigated for their TNF‐α responsiveness ex vivo in the periparturient period. Heparin‐stabilized blood samples were collected seven times over a period of 4 months (weeks −3, −1, 2, 3, 5, 9 and 13 around calving) and stimulated with 5 g/ml of E. coli LPS. Indeed, fluctuations in the TNF‐α responsiveness occurred over time. Moreover, the mean TNF‐α responsiveness of 38 cows was found to be significantly increased (P < 0.001) in the weeks close to calving. However, in the more stabile physiological periods, some cows had a consistently low TNF‐α response, whereas others had high a TNF‐α response. We are currently investigating whether high and low TNF‐α responders to E. coli LPS also exist in dairy cows in vivo. Moreover, the importance of TNF‐α responsiveness ex vivo to dairy cows' susceptibility and clinical response to experimental E. coli infections in the udder is being investigated.


id: cord-023429-x52gbklw
title: Mannan‐Binding Lectin Inhibits Humoural Responses
author: Ruseva, M.
date: 2008-06-28
txt: ./txt/cord-023429-x52gbklw.txt
cache: ./cache/cord-023429-x52gbklw.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169581/
doi: 10.1111/j.0300-9475.2004.01423an.x
summary:
[cell repeats an earlier one in this file: 994 characters]

abstract:
  Chronic hepatitis B virus (HBV) infection affects about 200–400 million people worldwide and represents one of the leading causes for liver cirrhosis and hepatocellular carcinoma. Control over the HBV infection is achieved mainly by vaccination with Hepatitis B surface antigen (HBsAg). HBsAg contains N‐linked glycosylation side and is recognized by both MBL‐A and MBL‐C in a Ca‐dependent manner. HbsAg–MBL complexes activate complement and may thus affect humoural immunity. To investigate the role of MBL in humoural responses to HBsAg, we immununized mice that lack both MBL‐A and MBL‐C proteins with soluble HBsAg. It has been shown that deficiencies in other complement components like C1q, C4 and C3 result in decreased antibody responses. However, MBL double KO animals mounted dramatically increased humoural responses. After priming, MBL double KOs mounted HbsAg‐specific IgM responses, which were threefold higher than WT controls. After boosting the HBsAg, total IgG was 10‐fold higher in MBL KO than in WT control animals. Similar to the response to HbsAg, other glycosylated soluble antigens (e.g. invertase) induced better humoural responses in MBL double KO animals, suggesting that MBL plays an important role in a negative feedback regulation of adaptive immunity. Reconstitution experiments with rMBL partially rescued the KO phenotype. We propose that the clearance of glycoprotein antigens in MBL KO is handled differently from the WT, resulting in better stimulation of humoural responses. Alternatively, glycoprotein‐Ag‐MBL‐rich complexes inhibit B‐cell responsiveness via putative MBL receptors.


id: cord-023430-5zuewjv2
title: Interleukin‐18 Inhibition of Oral Carcinoma Cell Proliferation
author: Nilkaeo, A.
date: 2008-06-28
txt: ./txt/cord-023430-5zuewjv2.txt
cache: ./cache/cord-023430-5zuewjv2.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169582/
doi: 10.1111/j.0300-9475.2004.01423bg.x
summary:
[cell repeats an earlier one in this file: 994 characters]

abstract:
  Interleukin‐18 (IL‐18), a pro‐inflammatory cytokine that is produced by both lymphoid and nonlymphoid cells, has a critical role in modulation of innate and adaptive immunity. Its primary function in stimulation of IFN‐γ production and stimulation of NK‐cell‐cytotoxic activities makes this cytokine a candidate for cancer immunotherapy. In oral cavity, this cytokine is produced by oral epithelia and carcinoma cells and is related to tumour regression in nude mice bearing salivary adenocarcinoma. However, direct effects of this cytokine on oral cancer cells have not been elucidated. In this project, we investigated IL‐18 effect on an oral carcinoma (KB) cell line. With RT‐PCR technique, KB‐cell line was found to express IL‐18 receptors (IL‐18Rα and IL‐18Rβ), indicating that this oral carcinoma line is a target for IL‐18 study. We showed that recombinant human IL‐18 inhibited KB‐cell proliferation by 17% at concentration of 100 ng/ml (P < 0.05), whereas LDH release by these cells in treatment group and control groups was comparable, indicating that IL‐18 suppression of cell proliferation was not mediated by the induction of cell death. To further address this hypothesis, we found that IL‐18 treatment did not induce apoptotic cell death, as studied by DNA laddering and TUNEL assays. In addition, expression pattern of cell death‐controlling genes (bcl‐2 and bax) was not altered by this cytokine. Findings in these studies indicated that suppression of KB‐cell proliferation may be attributed to control of cell cycle, growth arrest or induction of cell differentiation. The data presented in this project could provide an insight of how cancer cell directly responds to IL‐18, as this cytokine is an important regulator of anticancer mechanisms.


id: cord-023431-zjyrhlxn
author: Sigmundsdóttir, H.
date: 2008-06-28
txt: ./txt/cord-023431-zjyrhlxn.txt
cache: ./cache/cord-023431-zjyrhlxn.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169583/
doi: 10.1111/j.0300-9475.2004.01423ab.x
summary:
[cell repeats an earlier one in this file: 994 characters]

title:
  Differential Effects of Interleukin‐12 and Interleukin‐10 on Superantigen‐Induced Expression of Cutaneous Lymphocyte‐Associated Antigen and αEβ7 Integrin (CD103) by CD8(+) T cells

abstract:
  The interaction with adhesion molecules expressed by vascular endothelium is the first step in lymphocyte infiltration into tissues. At both cutaneous and mucosal sites interleukin‐10 (IL‐10), IL‐12 and transforming growth factor (TGF)‐β are important regulators of chronic inflammatory disease, where cutaneous lymphocyte‐associated antigen (CLA) and αE integrin (CD103) may be expressed. Unlike CLA, CD103 is not believed to play a role in tissue‐specific homing but may help to retain T cells within epithelial layers. We have previously shown that IL‐12 alone can together with an unknown cofactor increase the expression of CLA. Stimulation with streptococcal pyrogenic exotoxin C (SpeC) increased the expression of CD103 by CD8(+) but not CD4(+) T cells. While IL‐12 increased superantigen‐stimulated expression of CLA, this cytokine strongly inhibited the CD103 expression, and a combination of IL‐12 and TGF‐β completely abrogated the induced CD103 expression. Conversely, IL‐10 suppressed CLA but increased CD103 expression. These findings indicate that, in addition to suppressing the development of Th1‐mediated inflammatory responses, IL‐10 may also inhibit the migration of CD8(+) T cells into the skin while IL‐12 promotes such migration. Thus, the expression of CLA and CD103 may be antagonistically regulated by IL‐10 and IL‐12, and the balance between these cytokines could influence the T‐cell migration of inflammatory cells into epithelial tissues.


id: cord-023433-d1b7qvhs
title: Expression of Human Collectins in Colorectal Carcinoma
author: Siassi, M.
date: 2008-06-28
txt: ./txt/cord-023433-d1b7qvhs.txt
cache: ./cache/cord-023433-d1b7qvhs.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169588/
doi: 10.1111/j.0300-9475.2004.01423bo.x
summary:
[cell repeats an earlier one in this file: 994 characters]

abstract:
  Introduction: The human collectins, mannan‐binding lectin (MBL), surfactant protein‐A (SP‐A) and surfactant‐protein‐D (SP‐D) play a central role in the innate immune system. Immunological responses to malignant transformation of epithelial cells gained increasing interest recently. A former study could demonstrate binding of MBL to certain colorectal carcinoma (CRC) cell lines in vitro. We therefore examined the expression of human collectins in normal colon mucosa and in colorectal carcinomas. Materials and methods: Colon samples from 20 CRC patients and 10 normal mucosa samples were collected immediately after surgery. The tissue was microdissected and RNA isolated (Qiagen, Rneasy‐Kit). Gene expression profiles were analysed using Gene‐chips (Affymetrix, HG‐U133). We analysed the data for the expression of MBL, its associated serine proteases mannan‐binding lectin‐associated serine protease 1/2 (MASP 1/2), SP‐A and SP‐D. The signal intensity of the genes of interest was compared using the Mann–Whitney U‐test. Results: The expression of human collectins in normal human colon mucosa was generally low. Only the expression of SP‐A and MASP‐2 reached the noise threshold of 250 signals. These genes were significantly downregulated in CRC specimens. The expression of the other proteins showed no difference in normal mucosa and CRC. Conclusion: As demonstrated before, the expression of human collectins in normal colon was low in this study. Only SP‐A showed a significant expression in normal mucosa which was downregulated in CRC. As the absolute signal level was below the noise threshold, these results have to be interpreted with caution and require confirmation by direct measurenment of the proteins. Our results suggest that there is no major role for the human collectins in colorectal cancer.


id: cord-023438-g0k0vvdc
author: Krog, J.
date: 2008-06-28
txt: ./txt/cord-023438-g0k0vvdc.txt
cache: ./cache/cord-023438-g0k0vvdc.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169595/
doi: 10.1111/j.0300-9475.2004.01423aa.x
summary:
[cell repeats an earlier one in this file: 994 characters]

title:
  The Effects of Hyperbaric Exposure on Human Peripheral Blood Mononuclear Cells, with Special Emphasis on Natural Killer Cell Cytotoxicity and Subsets

abstract:
  Materials and methods: As an experimental physiological stress model, we examined the effects of hyperbaric exposure on peripheral blood mononuclear cells (PBMCs) obtained from venous blood drawn from eight divers during a simulated heliox saturation dive. Eight persons working in normobar atmosphere outside the pressurized chamber served as control donors. The spontaneous cytotoxicity of the PBMCs was estimated in a 4 h 51Cr‐release assay using k562 as NK‐sensitive target cells. The PBMCs were characterized, using 4‐colour flow cytometry, with special emphasis on the NK‐cell subsets. The data were statistically analysed using a multivariate regression model (Stata 8.2). P values <0.05 was considered statistically significant. Results: The estimated cytotoxicity increased significantly in both the group of divers and control donors during the dive (pdivers < 0.01 and pcontrols < 0.01). Although the cytotoxicity increased relatively more (P < 0.01) in the group of divers compared to the group of control donors between day 1 and 2. Discussion: The increased cytotoxicity of PBMC estimated in the group of divers indicate that parts of the cellular immune system are affected during the extreme physiological conditions induced during the initial phase of the presented experimental hyperbaric setup. The increase in cytotoxicity observed in the group of control donors could hypothetically reflect the stress level in persons working outside the pressurized chamber during the dive.


id: cord-023439-r04y1j22
author: Hedegaard, C. J.
date: 2008-06-28
txt: ./txt/cord-023439-r04y1j22.txt
cache: ./cache/cord-023439-r04y1j22.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169603/
doi: 10.1111/j.0300-9475.2004.01423k.x
summary:
  We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients.

title:
  The Role of Immune Complexes Consisting of Myelin Basic Protein (MBP), Anti‐MBP Antibodies and Complement in Promoting CD4(+) T‐cell Responses to MBP in Health and Multiple Sclerosis

abstract:
  Multiple sclerosis (MS) is an autoimmune condition characterized by degeneration of nerve fibre myelin sheets. A candidate autoantigen, myelin basic protein (MBP), has especially attracted attention. The presence of anti‐MBP antibodies is a predictor of definite MS, but their role in the pathogenesis remains obscure. T cells have long been known to play a pivotal role in the pathogenesis of MS. Recently, an important role for B cells as autoantigen‐presenting cells has been demonstrated in other autoimmune diseases, including rheumatoid arthritis and diabetes. The uptake of MBP by B cells and the presentation of MBP‐derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease‐associated anti‐MBP antibodies in MS patients, respectively. We have investigated the formation of MBP‐containing IC, the binding of MBP to B cells, the MBP‐elicited induction of Th‐cell and B‐cell proliferation and the cytokine production in peripheral blood mononuclear cells (PBMCs) from healthy donors grown in the presence of intact or C‐inactivated serum from healthy donors or patients with MS. While MBP did not induce measurable proliferation of B cells nor CD4(+) T cells, we observed the production of TNF‐α, IFN‐γ and IL‐10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. By contrast, no production of IL‐2, IL‐4 and IL‐5 was detected. We are currently investigating the capability of MS sera to promote the formation of MBP‐containing IC and thereby enhance the cytokine responses, by virtue of elevated anti‐MBP contents.


id: cord-023441-q83y12sk
title: Recominant Expression and Immunological Characterization of House Dust Mite Allergen Der P 1
author: Draborg, H.
date: 2008-06-28
txt: ./txt/cord-023441-q83y12sk.txt
cache: ./cache/cord-023441-q83y12sk.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169606/
doi: 10.1111/j.0300-9475.2004.01423ag.x
summary:
[cell repeats an earlier one in this file: 994 characters]

abstract:
  The cysteine protease Der p1 from dust mite of the genus Dermatophagoides pteronyssinus is a major type I allergen. About 80% of house dust mite (HDM) allergic individuals are reactive to this protease in standard assays for detection of IgE. A curative treatment for atopic allergy is immunotherapy (IT) with HDM extracts which are complex mixtures occasionally resulting in anaphylactic reactions. Novozymes focuses on developing a recombinant variant of Der p1 which exhibit lowered risk of IgE‐mediated allergic reactions, while maintaining its ability to trigger proper Th‐cell responses. This may provide a safer alternative for specific IT of HDM allergy. A secreted recombinant form of pro‐Der p 1 expressed by Saccharamyces cerevisiae was obtained by fusion of the pro‐enzyme to a fungal signal peptide. The N‐glycosylation site of Der p1 was mutated resulting in a deglycosylated pro‐enzyme with a molecular mass of 35 kDa. Protein purification procedure was developed to obtain nearly pure Der p1 protein followed by determination of concentration by active‐site‐titration with the cysteine protease inhibitor E64. The deglycosylated recombinant pro‐Der p 1 revealed immunologic similarity to the native Der p 1 molecule when compared in basophile histamine release, IgE‐binding assays and T‐cell proliferation assays. By in silico epitope mapping of a modelled 3‐dimensional structure of Der p1, five putative IgG and IgE epitopes were predicted. By protein engineering, the predicted epitopes were removed one by one in Der p1 and screening for hypoallergenic variants was performed.


id: cord-023445-c4tqioz1
author: Lauridsen, C.
date: 2008-06-28
txt: ./txt/cord-023445-c4tqioz1.txt
cache: ./cache/cord-023445-c4tqioz1.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169619/
doi: 10.1111/j.0300-9475.2004.01423u.x
summary:
[cell repeats an earlier one in this file: 994 characters]

title:
  Supplementation of Vitamin C to Weaner Diets Increases IgM Concentration and Improves the Biological Activity of Vitamin E in Alveolar Macrophages

abstract:
  Vitamins E and C have been found to increase the cellular and humeral immunity of pigs. Vitamin E deficiency has also been found to predispose pigs to different diseases, E. coli infection is one among them. After weaning, the vitamin E status of pigs often decreases to a critical low level. In this experiment, we studied whether vitamin C supplementation would be a possible feeding strategy to optimize the immune status of weaners. The interaction between vitamin E and C is interesting due to the reported sparing action on vitamin E or synergism between these to vitamins. Piglets were weaned at day 28 of age from sows fed increasing dietary vitamin E during lactation, and piglets were during the following 3 weeks fed either a control diet or this diet supplemented with 500 mg STAY‐C per kg. Blood sampling was obtained weekly from day 28 and until day 49 of age. On the same days, one piglet per dietary treatment was killed and alveolar macrophages (AM) were harvested. Vitamin C supplementation increased the concentration of IgM in serum of piglets throughout the weaning period. Although the vitamin E concentration in AM decreased with increasing age of the piglets, the concentration was numerically higher in piglets of sows fed the high dietary level of vitamin E. However, vitamin C supplementation tended to increase the total AM concentration of vitamin E after weaning and increased the proportion of the biologically most active isomer of vitamin E [RRR‐(α‐tocopherol)] in the AM. The eicosanoid synthesis by AM was not influenced by the vitamin C supplementation, but the synthesis of leukotriene B4 was decreased 2 weeks after weaning compared to other days of AM harvesting. In conclusion, dietary vitamin C supplementation improved the immune responses of piglets after weaning.


id: cord-256769-flfycl7i
title: Complement and Viral Pathogenesis
author: Stoermer, Kristina A.
date: 2011-03-01
txt: ./txt/cord-256769-flfycl7i.txt
cache: ./cache/cord-256769-flfycl7i.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0042682210008135
doi: 10.1016/j.virol.2010.12.045
summary:
  Taken together, these studies and the findings that multiple components of the complement pathway are required for mice to survive ectromelia virus infection (discussed below), indicate that complement activation and viral evasion of the complement system are critical determinants of poxvirus pathogenesis. Mice deficient in C3, C4, or CR2 (which in mice encodes both CR1 and CR2) had significantly diminished IgG responses following Herpes Simplex virus-1 (HSV-1) infection, suggesting that activation of the classical pathway plays a key role in regulating the antibody response to HSV-1 infection (Da Costa et al., 1999) . Unlike VSV infection, the genetic absence of C3 or CR2 resulted in increased WNV-induced mortality, earlier WNV entry into the central nervous system, and greater viral loads of WNV in the brains of mice, suggesting complement-mediated regulation of B cell responses was critical to control WNV dissemination, replication, and disease (Mehlhop et al., 2005) .

abstract:
  The complement system functions as an immune surveillance system that rapidly responds to infection. Activation of the complement system by specific recognition pathways triggers a protease cascade, generating cleavage products that function to eliminate pathogens, regulate inflammatory responses, and shape adaptive immune responses. However, when dysregulated, these powerful functions can become destructive and the complement system has been implicated as a pathogenic effector in numerous diseases, including infectious diseases. This review highlights recent discoveries that have identified critical roles for the complement system in the pathogenesis of viral infection.


id: cord-266739-oay8gbit
author: Eisen, Damon P.
date: 2011-11-30
txt: ./txt/cord-266739-oay8gbit.txt
cache: ./cache/cord-266739-oay8gbit.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0198885911005040
doi: 10.1016/j.humimm.2011.08.014
summary:
  title: No association between mannose-binding lectin deficiency and H1N1 2009 infection observed during the first season of this novel pandemic influenza virus Therefore, we studied whether MBL deficiency played a role in infection with the novel H1N1 2009 influenza strain in exposed health care workers. This is countered, however, by the in vitro evidence of MBL''s inhibition of influenza virus [3, 18] , recent evidence of MBL''s role in the development of humoral immunity to influenza [19] , and clinical association studies that demonstrate that MBL deficiency predisposes not only to respiratory tract infection in general, but also to respiratory tract infections with viral pathogens like severe acute respiratory syndrome in particular [7] . Although we have not demonstrated a clinical association between MBL deficiency and predisposition to the novel H1N1 2009 influenza strain, this may be because of the absence of exposed MBL-binding sites on this specific virus.

title:
  No association between mannose-binding lectin deficiency and H1N1 2009 infection observed during the first season of this novel pandemic influenza virus

abstract:
  Abstract Genetic variations in host immunity may influence susceptibility to novel infections like the recently emergent pandemic influenza virus. Prior studies demonstrated that mannose-binding lectin (MBL) inactivates influenza. Furthermore, MBL deficiency is common and appears to predispose to respiratory virus infections. Therefore, we studied whether MBL deficiency played a role in infection with the novel H1N1 2009 influenza strain in exposed health care workers. In a nested case–control study, we observed no association between phenotypic MBL deficiency, variously defined, and predisposition to H1N1 2009 influenza in 63 pairs of seropositive and seronegative participants. MBL appears to currently have little impact on innate immune responses to H1N1 2009 influenza.


id: cord-268902-npug5c8p
title: The Roles of Direct Recognition by Animal Lectins in Antiviral Immunity and Viral Pathogenesis
author: Liu, Yang
date: 2015-01-29
txt: ./txt/cord-268902-npug5c8p.txt
cache: ./cache/cord-268902-npug5c8p.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/25642837/
doi: 10.3390/molecules20022272
summary:
  In agreement with the findings in mosquitoes, a recent study has identified a C-type lectin in the shrimp Marsupenaeus japonicus that interacts with an envelope protein of White spot syndrome virus (WSSV) and consequently associates with a cell-surface calreticulin, which serves as a membrane receptor that facilitates viral entry in a cholesterol-dependent manner [128] . The interaction between lectins and viral glycoproteins may lead to the three following consequences: (1) lectins, such as MBL and SPs, function as pattern recognition molecules that bind a repertoire of viruses and activate antiviral immune responses; (2) lectins are employed as attachment factors that recruit viral particles to the cell membrane to enhance viral entry, e.g., some mammalian lectins (DC-SIGN, L-SIGN, MR and MPRs) or their homologs in arthropods (mosGCTLs); and (3) some intracellular lectins, such as calnexin and ERGIC-53, function as susceptibility factors associated with virus-encoded proteins to facilitate viral replication or assembly (please refer to Figures 1 and 4) .

abstract:
  Lectins are a group of proteins with carbohydrate recognition activity. Lectins are categorized into many families based on their different cellular locations as well as their specificities for a variety of carbohydrate structures due to the features of their carbohydrate recognition domain (CRD) modules. Many studies have indicated that the direct recognition of particular oligosaccharides on viral components by lectins is important for interactions between hosts and viruses. Herein, we aim to globally review the roles of this recognition by animal lectins in antiviral immune responses and viral pathogenesis. The different classes of mammalian lectins can either recognize carbohydrates to activate host immunity for viral elimination or can exploit those carbohydrates as susceptibility factors to facilitate viral entry, replication or assembly. Additionally, some arthropod C-type lectins were recently identified as key susceptibility factors that directly interact with multiple viruses and then facilitate infection. Summarization of the pleiotropic roles of direct viral recognition by animal lectins will benefit our understanding of host-virus interactions and could provide insight into the role of lectins in antiviral drug and vaccine development.


id: cord-278644-u4swxsjj
title: MAp19, the alternative splice product of the MASP2 gene
author: Degn, Søren E.
date: 2011-10-28
txt: ./txt/cord-278644-u4swxsjj.txt
cache: ./cache/cord-278644-u4swxsjj.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/21871896/
doi: 10.1016/j.jim.2011.08.006
summary:
  Strips of a Western blot containing purified MBL/MASP complexes from human plasma were developed using hybridoma supernatants as primary antibodies. Strips were incubated with hybridoma supernatants diluted 1/10 in primary buffer (TBS/Tw, 1 mM EDTA, with 1 mg HSA and 100 μg normal human IgG (hIgG) added per ml), or with the parental rat serum 1/500. The wells were then blocked with HSA, 1 mg/ml TBS, washed thrice with TBS/Tw, and incubated with serum samples diluted 20-fold in MAp19 buffer (TBS/Tw, 1 M total NaCl, 10 mM EDTA, containing 100 μg ΔhIgG (heat-aggregated hIgG); Beriglobin, from ZLB Behring GmbH, incubated 30 min at 63°C and centrifuged 10 min at 3,000 g to remove large aggregates) per ml, and 100 μg normal rat IgG (Lampire) per ml) o.n. at RT. The specificity of the anti-MAp19 antibodies was validated by performing Western blotting with purified MBL/MASP complex (Fig. 1C) .

abstract:
  Abstract The lectin pathway of complement is a central part of innate immunity, but as a powerful inducer of inflammation it needs to be tightly controlled. The MASP2 gene encodes two proteins, MASP-2 and MAp19. MASP-2 is the serine protease responsible for lectin pathway activation. The smaller alternative splice product, MAp19, lacks a catalytic domain but retains two of three domains involved in association with the pattern-recognition molecules (PRMs): mannan-binding lectin (MBL), H-ficolin, L-ficolin and M-ficolin. MAp19 reportedly acts as a competitive inhibitor of MASP-2-mediated complement activation. In light of a ten times lower affinity of MAp19, versus MASP-2, for association with the PRMs, much higher serum concentrations of MAp19 than MASP-2 would be required for MAp19 to exert such an inhibitory activity. Just four amino acid residues distinguish MAp19 from MASP-2, and these are conserved between man, mouse and rat. Nonetheless we generated monoclonal rat anti-MAp19 antibodies and established a quantitative assay. We found the concentration of MAp19 in serum to be 217ng/ml, i.e., 11nM, comparable to the 7nM of MASP-2. In serum all MASP-2, but only a minor fraction of MAp19, was associated with PRMs. In contrast to previous reports we found that MAp19 could not compete with MASP-2 for binding to MBL, nor could it inhibit MASP-2-mediated complement activation. Immunohistochemical analyses combined with qRT-PCR revealed that both MAp19 and MASP-2 were mainly expressed in hepatocytes. High levels of MAp19 were found in urine, where MASP-2 was absent.


id: cord-282433-p6jl9gxf
author: Tu, Xinyi
date: 2015-03-27
txt: ./txt/cord-282433-p6jl9gxf.txt
cache: ./cache/cord-282433-p6jl9gxf.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.jinf.2015.03.006
doi: 10.1016/j.jinf.2015.03.006
summary:
  RESULTS: Both the high-CCL2-producing GG genotype and the low-MBL-producing B allele were consistently associated with increased risks of SARS-CoV infection in all 4 case–control populations (joint P = 1.6 × 10(−4) and 4.9 × 10(−8), for CCL2 and MBL respectively), with no interaction between polymorphisms could be detected. 3À10 In particular, our previous two independent association studies have implicated that a functional polymorphism at codon 54 in exon 1 (rs1800450, G230A, denoted as A/B variant) of mannose binding lectin (MBL), which encodes a protein belonging to the family of collectin and plays a critical role in the innate immune response, conferred a significantly increased susceptibility to SARS-CoV infection. Taken together, the large size of the investigation, the consistency of the observations in 4 independent caseecontrol series and the low P values distinguish our study from previous studies investigating the influence of different other polymorphisms on the development of SARS, and strengthen the association between the CCL2 G-2518A and MBL codon 54 variant (A/B) and susceptibility to SARS-CoV infection.

title:
  Functional polymorphisms of the CCL2 and MBL genes cumulatively increase susceptibility to severe acute respiratory syndrome coronavirus infection

abstract:
  OBJECTIVES: To assess associations between the functional polymorphisms G-2518A at the chemokine (C–C motif) ligand 2 gene (CCL2) and mannose binding lectin (MBL) codon 54 variant (A/B) and susceptibility to SARS. METHODS: We genotyped the CCL2 G-2518A and MBL codon 54 variant (A/B) in 4 case–control populations of Chinese descent, totally consisting of 932 patients with SARS and 982 control subjects. RESULTS: Both the high-CCL2-producing GG genotype and the low-MBL-producing B allele were consistently associated with increased risks of SARS-CoV infection in all 4 case–control populations (joint P = 1.6 × 10(−4) and 4.9 × 10(−8), for CCL2 and MBL respectively), with no interaction between polymorphisms could be detected. Furthermore, all the 4 case–control studies demonstrated a cumulative effect on risk of SARS-CoV infection for the combination of polymorphisms (joint P = 1.3 × 10(−10)). However, tests using the area under the curve (AUC) indicated that at this stage, the polymorphisms were unlikely to be appropriate for risk prediction testing because of low AUC values (all <66%). Additionally, no association was observed between the polymorphisms and severity of SARS. CONCLUSIONS: The CCL2 G-2518A and MBL codon 54 variant have a significantly cumulative effect on increased risk of SARS-CoV infection.


id: cord-292581-6ipzvryb
title: Elevated levels of vitamin D and deficiency of mannose binding lectin in dengue hemorrhagic fever
author: Alagarasu, Kalichamy
date: 2012-05-04
txt: ./txt/cord-292581-6ipzvryb.txt
cache: ./cache/cord-292581-6ipzvryb.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/22559908/
doi: 10.1186/1743-422x-9-86
summary:
  BACKGROUND: Altered plasma concentrations of vitamin D and mannose binding lectin (MBL), components of innate immunity, have been shown to be associated with the pathogenesis of viral infections. The objective of the present study was to find out whether plasma concentrations of MBL and vitamin D are different in patients with dengue fever (DF) and dengue hemorrhagic fever (DHF). Therefore, we investigated the levels of plasma vitamin D and MBL in dengue infected patients in the context of disease severity and immune status. When the patients were grouped based on immune status and disease severity, secondary DHF cases had significantly higher concentrations of vitamin D as compared to secondary DF cases (P < 0.050). Analysis of circulating concentrations of MBL in dengue cases and healthy controls revealed no significant difference between the two groups suggesting that the MBL mediated pathway of complement activation might be inhibited or may not be induced during DENV infection.

abstract:
  BACKGROUND: Altered plasma concentrations of vitamin D and mannose binding lectin (MBL), components of innate immunity, have been shown to be associated with the pathogenesis of viral infections. The objective of the present study was to find out whether plasma concentrations of MBL and vitamin D are different in patients with dengue fever (DF) and dengue hemorrhagic fever (DHF). THE RESULTS: The plasma concentrations of vitamin D and MBL were assessed in 48 DF cases, 45 DHF cases and 20 apparently healthy controls using ELISA based methods. Vitamin D concentrations were found to be higher among both DF and DHF cases as compared to healthy controls (P < 0.005 and P < 0.001). Vitamin D concentrations were not different between DF and DHF cases. When the dengue cases were classified into primary and secondary infections, secondary DHF cases had significantly higher concentrations of vitamin D as compared to secondary DF cases (P < 0.050). MBL concentrations were not significantly different between healthy controls and dengue cases. MBL concentrations were observed to be lower in DHF cases as compared to DF cases (P < 0.050). Although MBL levels were not different DF and DHF cases based on immune status, the percentage of primary DHF cases (50%) having MBL levels lower than 500 ng/ml were less compared to primary DF cases (P = 0.038). CONCLUSIONS: The present study suggests that higher concentrations of vitamin D might be associated with secondary DHF while deficiency of MBL may be associated with primary DHF.


id: cord-304626-ffao7vka
title: Viral Evasion of the Complement System and Its Importance for Vaccines and Therapeutics
author: Mellors, Jack
date: 2020-07-09
txt: ./txt/cord-304626-ffao7vka.txt
cache: ./cache/cord-304626-ffao7vka.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fimmu.2020.01450
doi: 10.3389/fimmu.2020.01450
summary:
  A better understanding of this virus-host interplay and its contribution to pathogenesis has previously led to: the identification of genetic factors which influence viral infection and disease outcome, the development of novel antivirals, and the production of safer, more effective vaccines. Infected host cells which present viral antigens on the cell surface membrane can activate the classical pathway, as the antigens bind IgM/IgG to induce complement dependent cytotoxicity (CDC). Non-neutralizing antibodies can still bind the viral target with the potential to cross-link with Fc receptors, or activate complement and interact with complement receptors, to enhance viral infection of host cells (241) . Use of the non-neutralizing influenza virus M2 extracellular vaccine in mice required functional C3 to confer protection and induce effective humoral and cell-mediated immune responses (245) .

abstract:
  The complement system is a key component of innate immunity which readily responds to invading microorganisms. Activation of the complement system typically occurs via three main pathways and can induce various antimicrobial effects, including: neutralization of pathogens, regulation of inflammatory responses, promotion of chemotaxis, and enhancement of the adaptive immune response. These can be vital host responses to protect against acute, chronic, and recurrent viral infections. Consequently, many viruses (including dengue virus, West Nile virus and Nipah virus) have evolved mechanisms for evasion or dysregulation of the complement system to enhance viral infectivity and even exacerbate disease symptoms. The complement system has multifaceted roles in both innate and adaptive immunity, with both intracellular and extracellular functions, that can be relevant to all stages of viral infection. A better understanding of this virus-host interplay and its contribution to pathogenesis has previously led to: the identification of genetic factors which influence viral infection and disease outcome, the development of novel antivirals, and the production of safer, more effective vaccines. This review will discuss the antiviral effects of the complement system against numerous viruses, the mechanisms employed by these viruses to then evade or manipulate this system, and how these interactions have informed vaccine/therapeutic development. Where relevant, conflicting findings and current research gaps are highlighted to aid future developments in virology and immunology, with potential applications to the current COVID-19 pandemic.


id: cord-304718-w469n0o8
title: Lack of association between polymorphisms of MASP2 and susceptibility to SARS coronavirus infection
author: Wang, Yan
date: 2009-05-01
txt: ./txt/cord-304718-w469n0o8.txt
cache: ./cache/cord-304718-w469n0o8.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1186/1471-2334-9-51
doi: 10.1186/1471-2334-9-51
summary:
  One case-control study has reported an association between susceptibility to SARS and mannan-binding lectin (MBL) in China. As the downstream protein of MBL, variants of the MBL-associated serine protease-2 (MASP2) gene may be associated with SARS coronavirus (SARS-CoV) infection in the same population. RESULTS: There is no significant association between alleles or genotypes of the MASP2 tagSNP and susceptibility to SARS-CoV in both Beijing and Guangzhou populations. A few case-control studies have reported an association between SARS susceptibility and human leucocyte antigen (HLA) and MBL [8] [9] [10] [11] . With regard to SARS-CoV infection, the codon 54 variant of the MBL gene has been shown to be associated with infection susceptibility but not with disease severity [11] . As the downstream protein of MBL, variants of the MASP2 gene may be associated with SARS-CoV infection. Genomic DNA from 30 individuals with SARS was chosen for analysis of MASP2 gene polymorphisms.

abstract:
  BACKGROUND: The pathogenesis of severe acute respiratory disease syndrome (SARS) is not fully understood. One case-control study has reported an association between susceptibility to SARS and mannan-binding lectin (MBL) in China. As the downstream protein of MBL, variants of the MBL-associated serine protease-2 (MASP2) gene may be associated with SARS coronavirus (SARS-CoV) infection in the same population. METHODS: Thirty individuals with SARS were chosen for analysis of MASP2 polymorphisms by means of PCR direct sequencing. Tag single nucleotide polymorphisms (tagSNPs) were chosen using pairwise tagging algorithms. The frequencies of four tag SNPs (rs12711521, rs2261695, rs2273346 and rs7548659) were ascertained in 376 SARS patients and 523 control subjects, using the Beckman SNPstream Ultra High Throughput genotyping platform. RESULTS: There is no significant association between alleles or genotypes of the MASP2 tagSNP and susceptibility to SARS-CoV in both Beijing and Guangzhou populations. Diplotype (rs2273346 and rs12711521)were analyzed for association with susceptibility to SARS, no statistically significant evidence of association was observed. The Beijing and Guangzhou sample groups were homogeneous regarding demographic and genetic parameters, a joined analysis also showed no statistically significant evidence of association. CONCLUSION: Our data do not suggest a role for MASP2 polymorphisms in SARS susceptibility in northern and southern China.


id: cord-306111-wn1gxhk9
title: Mannose‐binding lectin in innate immunity: past, present and future
author: Dommett, R. M.
date: 2006-09-01
txt: ./txt/cord-306111-wn1gxhk9.txt
cache: ./cache/cord-306111-wn1gxhk9.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/16948640/
doi: 10.1111/j.1399-0039.2006.00649.x
summary:
  Third MBL mutation in codon 52 (variant D) described (52) 1995 Polymorphisms found in promoter region of MBL gene (55) 1997 Second MASP found to activate complement (20) MBL mutations are an important risk factor for infections in children (132) 1998 Reconstitution of opsonizing activity by infusion of purified MBL into MBL-deficient humans (112) 1999 Truncated form of MASP-2 -MAp19 (21) 2000 Complement-activating complex of ficolins and MASP (133) MBL shown to bind to clinically relevant organisms (15) Structural aspects of MBL

abstract:
  The human collectin, mannose‐binding lectin (MBL), is an important protein of the humoral innate immune system. With multiple carbohydrate‐recognition domains, it is able to bind to sugar groups displayed on the surfaces of a wide range of microorganisms and thereby provide first‐line defence. Importantly, it also activates the complement system through a distinctive third pathway, independent of both antibody and the C1 complex. Three single point mutations in exon 1 of the expressed human MBL‐2 gene appear to impair the generation of functional oligomers. Such deficiencies of functional protein are common in certain populations, e.g. in sub‐Saharan Africa, but virtually absent in others, e.g. indigenous Australians. MBL disease association studies have been a fruitful area of research and implicate a role for MBL in infective, inflammatory and autoimmune disease processes. Overall, there appears to be a genetic balance in which individuals generally benefit from high levels of the protein. However, in certain situations, reduced levels of circulating MBL may be beneficial to the host and this may explain the persistence of the deleterious gene polymorphisms in many population groups.


id: cord-310110-haukpwtf
author: Guo, Jinlei
date: 2015-02-27
txt: ./txt/cord-310110-haukpwtf.txt
cache: ./cache/cord-310110-haukpwtf.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/25634695/
doi: 10.1016/j.bbrc.2015.01.070
summary:
  title: Limited effect of recombinant human mannose-binding lectin on the infection of novel influenza A (H7N9) virus in vitro Our findings suggest that MBL, the host innate molecule, has differential interference effects with human and avian influenza virus and limited antiviral effect against H7N9 virus. Different concentrations of rhMBL were diluted in HBSS containing Ca 2þ and mixed with influenza virus in a total volume of 100 mL and preincubated at 37 C for 1 h, and then transferred to wells precoated with fetuin (Sigma, USA) and incubated at 37 C for 4 h, After washing, 100 mL of HRP-labeled peanut lectin (3 mg/mL) was added and after 1 h at room temperature, the wells were washed and o-phenylenediamine dihydrochloride in citrate buffer was added, reaction was stopped by 2 M H 2 SO 4 , and the OD at 492 nm was measured. Therefore, the strong MBL-H7N9 virus interaction whereas limited effects on viral HA-receptor binding or NA-mediated releasing, might amplify immune dysfunctions in vivo and confer clinical severity of H7N9 infection via activating complement pathway and further investigates are needed. Human mannan-binding lectin inhibits the infection of influenza A virus without complement

title:
  Limited effect of recombinant human mannose-binding lectin on the infection of novel influenza A (H7N9) virus in vitro

abstract:
  Abstract Mannose-binding lectin (MBL), a pattern-recognition molecule in serum, recognizes specific hexose sugars rich in mannose and N-acetylglucosamine on bacterium, yeasts, viruses as well as apoptotic cells. It has been well-identified that MBL has antiviral effects via binding to seasonal influenza H1 and H3 subtype viruses. Influenza A (H7N9) virus, a novel reassortant virus to human population, possesses the surface hemagglutinin (HA) and neuraminidase (NA) genes from duck and wild-bird influenza viruses and internal genes from poultry H9N2 viruses. As of Dec 7th, 2014, a total of 467 human infections and 183 fatal cases have been identified. Here, recombinant human (rh) MBL was tested for its binding and effects on hemagglutination inhibition (HI) and NA activity inhibition (NAI) of avian H7N9, H9N2 and human H3N2 viruses. We discovered that rhMBL exhibited a strong binding to H7N9 virus as human H3N2 did at high virus titers. However, it performed a significantly weaker HI activity effect on H7N9 comparing to those of H3N2 and H9N2, even at a much higher concentration (3.67 ± 0.33 vs. 0.026 ± 0.001 and 0.083 ± 0.02 μg/mL, respectively). Similarly, minor NAI effect of rhMBL, even at up to 10 μg/mL, was found on H7N9 virus while it displayed significant effects on both H3N2 and H9N2 at a lowest concentration of 0.0807 ± 0.009 and 0.0625 μg/mL, respectively. The HI and NAI effects of rhMBL were calcium-dependent and mediated by lectin domain. Our findings suggest that MBL, the host innate molecule, has differential interference effects with human and avian influenza virus and limited antiviral effect against H7N9 virus.


id: cord-311913-cplhq4k9
title: Association of mannose‐binding lectin gene polymorphisms with Kawasaki disease in the Japanese
author: SATO, Satoshi
date: 2009-11-23
txt: ./txt/cord-311913-cplhq4k9.txt
cache: ./cache/cord-311913-cplhq4k9.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/20374367/
doi: 10.1111/j.1756-185x.2009.01428.x
summary:
  Method: The frequencies of the genotypes, defined as mutations in codons 52, 54 and 57, and the functional promoter variants of the MBL were determined in 45 patients with KD. 11 MBL2 gene polymorphism at codon 54 has shown to be associated with systemic lupus erythematosus, 12,13 rheumatic disease, and common variable immunodeficiency. 10 In this study, the combination of codon-54 polymorphism and promoter variants in the MBL2 gene were significantly higher in the KD group than that in the control group (P < 0.05). This study has shown that, in a population of individuals born in Japan, having codon 54 variants in the MBL2 gene is significantly associated with susceptibility to KD but not with coronary arterial lesions. Association of mannose-binding lectin gene variation with disease severity and infections in a population-based cohort of systemic lupus erythematosus patients

abstract:
  Objective: Kawasaki disease (KD) is a systemic vasculitis in childhood; its etiology is unknown. The possibility that KD is an infectious disease has been discussed and investigated for decades, in light of the implication that infections are involved in the pathogenesis of KD. Young children rely on their innate immune system for protection against virus and micro‐organisms. Human mannose binding lectin (MBL) is a C‐type serum lectin synthesized by the liver as an acute phase protein and it plays an important role in the innate immune system. Here, we investigate the relationship between the MBL gene polymorphisms and the occurrence of KD in the Japanese population. Method: The frequencies of the genotypes, defined as mutations in codons 52, 54 and 57, and the functional promoter variants of the MBL were determined in 45 patients with KD. Results: The MBL codon‐54 polymorphism frequency of heterozygote (GGC/GAC) and promoter variants were significantly higher in the KD group than that in the control group (P < 0.05). Neither group showed codon 52 nor 57 polymorphisms. Conclusion: It is possible that mutations of the MBL gene might be related to the trigger of the pathogenesis of Kawasaki disease.


id: cord-322933-5xnxjqm5
title: Collectins: Innate Immune Pattern Recognition Molecules
author: Murugaiah, Valarmathy
date: 2020-03-10
txt: ./txt/cord-322933-5xnxjqm5.txt
cache: ./cache/cord-322933-5xnxjqm5.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/978-981-15-1580-4_4
doi: 10.1007/978-981-15-1580-4_4
summary:
  The following nine collectins have been identified to date: mannan-binding lectin (MBL), three bovine serum collectins, conglutinin, CL-43 and CL-46, lung surfactant proteins SP-A and SP-D, and more recently discovered collectins including, collectin kidney 1 (CL-K1, also called CL-11), collectin liver 1 (CL-L1, also called CL-10) and collectin placenta 1 (CL-P1 also called CL-12). Thus, the interaction between SIRP-α and SHP-1 negatively regulates P38-MAP kinase signalling, and stimulates NF-κB activity, and cells become resistant to TNF-mediated effects, such as apoptosis (1) C1qRp (CD93) (C1q receptor associated with phagocytosis stimulated by C1q, MBL or SP-A): but this has subsequently been shown not to bind any of these ligands. Pulmonary surfactant protein A mediates enhanced phagocytosis of Mycobacterium tuberculosis by a direct interaction with human macrophages Role of mannose-binding lectin in the innate defense against Candida albicans: enhancement of complement activation, but lack of opsonic function, in phagocytosis by human dendritic cells

abstract:
  Collectins are collagen-containing C-type (calcium-dependent) lectins which are important pathogen pattern recognising innate immune molecules. Their primary structure is characterised by an N-terminal, triple-helical collagenous region made up of Gly-X-Y repeats, an a-helical coiled-coil trimerising neck region, and a C-terminal C-type lectin or carbohydrate recognition domain (CRD). Further oligomerisation of this primary structure can give rise to more complex and multimeric structures that can be seen under electron microscope. Collectins can be found in serum as well as in a range of tissues at the mucosal surfaces. Mannanbinding lectin can activate the complement system while other members of the collectin family are extremely versatile in recognising a diverse range of pathogens via their CRDs and bring about effector functions designed at the clearance of invading pathogens. These mechanisms include opsonisation, enhancement of phagocytosis, triggering superoxidative burst and nitric oxide production. Collectins can also potentiate the adaptive immune response via antigen presenting cells such as macrophages and dendritic cells through modulation of cytokines and chemokines, thus they can act as a link between innate and adaptive immunity. This chapter describes the structure-function relationships of collectins, their diverse functions, and their interaction with viruses, bacteria, fungi and parasites.


id: cord-324840-ug5a9wx6
title: The Role of Mannose-Binding Lectin in Severe Sepsis and Septic Shock
author: De Pascale, Gennaro
date: 2013-10-02
txt: ./txt/cord-324840-ug5a9wx6.txt
cache: ./cache/cord-324840-ug5a9wx6.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1155/2013/625803
doi: 10.1155/2013/625803
summary:
  In a cohort of critically ill pediatric patients, Fidler and coworkers observed that MBL levels less than 1000 ng/mL, consistent with MBL-2 gene exon 1 polymorphisms, significantly increased the risk of developing systemic inflammatory response syndrome (SIRS) and progression to severe sepsis/septic shock [32] . The association between the deficiency of this protein and worse outcome during severe systemic infections (i.e., evolution to refractory septic shock) may be also related to the significant interaction between complement activation, inflammatory cytokines'' "storm", and coagulation cascade. Hence MBL, due to its pivotal role in the crosstalking among complement activation, coagulation, and systemic inflammation, may represent a key point for the understanding of the development of systemic severe infections, as interestingly investigated in animal models and clinical studies involving patients with severe sepsis/septic shock.

abstract:
  Severe sepsis and septic shock are a primary cause of death in patients in intensive care unit (ICU). Investigations upon genetic susceptibility profile to systemic complications during severe infections are a field of increasing scientific interest. Particularly when adaptive immune system is compromised or immature, innate immunity plays a key role in the immediate defense against invasive pathogens. Mannose-binding lectin (MBL) is a serum protein that recognizes a wide range of pathogenic microorganisms and activates complement cascade via the antibody-independent pathway. More than 30% of humans harbor mutations in MBL gene (MBL2) resulting in reduced plasmatic levels and activity. Increased risk of infection acquisition has been largely documented in MBL-deficient patients, but the real impact of this form of innate immunosuppression upon clinical outcome is not clear. In critically ill patients higher incidence and worse prognosis of severe sepsis/septic shock appear to be associated with low-producers haplotypes. However an excess of MBL activation might be also harmful due to the possibility of an unbalanced proinflammatory response and an additional host injury. Strategies of replacement therapies in critically ill patients with severe infections are under investigation but still far to be applied in clinical practice.


id: cord-342176-tewfm8it
author: Kjærup, Rikke M.
date: 2013-11-08
txt: ./txt/cord-342176-tewfm8it.txt
cache: ./cache/cord-342176-tewfm8it.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0171298513001964
doi: 10.1016/j.imbio.2013.10.013
summary:
  title: Adjuvant effects of mannose-binding lectin ligands on the immune response to infectious bronchitis vaccine in chickens with high or low serum mannose-binding lectin concentrations Chickens from two inbred lines (L10H and L10L) selected for high or low MBL serum concentrations, respectively, were vaccinated against IBV with or without the addition of the MBL ligands mannan, chitosan and fructooligosaccharide (FOS). Studies using these chicken sublines as well as outbred chickens have shown an inverse relationship between the MBL concentrations and the pathogen-specific antibody response (Juul-Madsen et al. However, MBL has an influence as the difference was more pronounced for the L10H chickens than L10L chickens for both the IBV-specific IgG antibody titres and the numbers of CD4−CD8␣+ and CD4−CD8␣− cells. Mannan-binding lectin (MBL) serum concentration in relation to propagation of infectious bronchitis virus (IBV) in chickens Crosstalk between innate and adaptive immune responses to infectious bronchitis virus after vaccination and challenge of chickens varying in serum mannose-binding lectin concentrations

title:
  Adjuvant effects of mannose-binding lectin ligands on the immune response to infectious bronchitis vaccine in chickens with high or low serum mannose-binding lectin concentrations

abstract:
  Mannose-binding lectin (MBL) plays a major role in the immune response as a soluble pattern-recognition receptor. MBL deficiency and susceptibility to different types of infections have been subject to extensive studies over the last decades. In humans and chickens, several studies have shown that MBL participates in the protection of hosts against virus infections. Infectious bronchitis (IB) is a highly contagious disease of economic importance in the poultry industry caused by the coronavirus infectious bronchitis virus (IBV). MBL has earlier been described to play a potential role in the pathogenesis of IBV infection and the production of IBV-specific antibodies, which may be exploited in optimising IBV vaccine strategies. The present study shows that MBL has the capability to bind to IBV in vitro. Chickens from two inbred lines (L10H and L10L) selected for high or low MBL serum concentrations, respectively, were vaccinated against IBV with or without the addition of the MBL ligands mannan, chitosan and fructooligosaccharide (FOS). The addition of MBL ligands to the IBV vaccine, especially FOS, enhanced the production of IBV-specific IgG antibody production in L10H chickens, but not L10L chickens after the second vaccination. The addition of FOS to the vaccine also increased the number of circulating CD4+ cells in L10H chickens compared to L10L chickens. The L10H chickens as well as the L10L chickens also showed an increased number of CD4−CD8α−γδ T-cells when an MBL ligand was added to the vaccine, most pronouncedly after the first vaccination. As MBL ligands co-administered with IBV vaccine induced differences between the two chicken lines, these results indirectly suggest that MBL is involved in the immune response to IBV vaccination. Furthermore, the higher antibody response in L10H chickens receiving vaccine and FOS makes FOS a potential adjuvant candidate in an IBV vaccine.


